cluster of excellence frankfurt macromolecular complexes

 

  • Example include light-switchable molecules designed for in-cell applications and time-resolved techniques to study RNA folding.

  • CEF scientists have done groundbreaking work to overcome some of these challenges and made major contributions to elucidating the structure, mechanisms and regulation of a
    number of important large complexes, including respiratory complex I,[3][4] rotary ATPases,[5][6][7][8] Antigenic peptide recognition on TAP was resolved by DNP-enhanced solid-state NMR spectroscopy.

  • Especially solid-state (MAS) NMR enables bridging the gap between ‘static’ structures and biochemical data by probing membrane proteins directly within the bilayer environment.

  • CEF Research Area A – Structure, mechanisms and dynamics of complexes in the membrane[edit] Biological membranes have a very important role in life processes as everything
    a cell needs to live, grow and respond has to either pass through or act on them.

  • CEF grew out of the long-standing collaborative research on membrane proteins and RNA molecules and strengthened research efforts in these fields by recruiting further scientists
    to Frankfurt/Main.

  • Aims CEF scientists set out to investigate the structure and function of large macromolecular complexes, in particular membrane proteins and their assemblies, complexes involved
    in signal transduction and quality control, and RNA-protein complexes.

  • [27][28][29] CEF researchers have developed mass spectrometry approaches specifically suitable for large membrane protein complexes.

  • [1][2] The five research areas of CEF included: (A) Structure, mechanisms and dynamics of complexes in the membrane, (B) Composition and dynamics of macromolecular complexes
    in quality control and signalling, (C) Dynamics of ribonucleic acid-protein-complexes, (D) Design of macromolecular complexes, and (E) Methods for studying macromolecular complexes.

  • [23] The progress in 3D structure determination of membrane proteins by X-ray crystallography and cryo electron microscopy has created an increasing demand and opportunity
    for in-depth mechanistic studies by magnetic resonance methods.

  • Due to the challenges intrinsic to membrane proteins, progress relies on the availability of techniques at the forefront of method development.

  • For example, fundamental contributions were made towards the structural and functional description of proteorhodopsin, a pentameric light-driven proton pump by groups within
    CEF.

  • [30] A team of CEF scientists resolved the mechanism of the subtype selectivity of human bradykinin receptors for their peptide agonists by integrating DNP-enhanced solid-state
    nuclear magnetic resonance with advanced molecular modeling and docking[31]

  • In the crowded conditions of the cell membrane, most membrane proteins associate into complex dynamic assemblies to carry out their various tasks.

  • Several groups of CEF have contributed to advances in understanding how ubiquitin signalling is not only used as a degradation signal but also involved in several other cellular
    processes p63[edit] Research on TP63, also known as p63, has shown that this protein plays essential roles both for the proliferation and differentiation of stratified epithelial tissues as well as for the surveillance of the genetic quality
    in female germ cells.

  • A particular focus of research in CEF has been on protein quality control mechanisms that are the basis for the autophagic and the ubiquitin/proteasomal pathways, the two
    cellular systems used to degrade faulty or superfluous proteins, complexes and organelles.

  • [58] CEF Research Area C – Dynamics of ribonucleic acid-protein-complexes[edit] Many discoveries including the identification of multiple classes of noncoding RNAs and regulatory
    RNA elements has broadened the perspective on RNA function from a passive carrier of information to an active cellular component.

  • A set of probes has been characterized and validated as tools for specific bromodomains[55] Interactions with soluble domains at the membrane[edit] CEF showed that vascular
    endothelial growth factor receptor-2 needs to be internalized and is regulated by its association to ephrin B2 in endothelial cells.

  • This isoform adopts a closed, inactive and only dimeric conformation in which both, the interaction with the DNA as well as with the transcriptional machinery is significantly
    reduced[47] The inhibition is achieved by blocking the tetramerization interface of the oligomerization domain with a six-stranded anti-parallel beta-sheet.

  • Work by a collaboration between several CEF groups unravelled the molecular nature of Bowen-Conradi syndrome by demonstrating that the disease-causing point mutation of the
    ribosome biogenesis factor Nep1 impairs its nucleolar localisation and RNA binding.

  • In humans, there are six different proteins, which play a central role by connecting nascent autophagosome membranes and cargo-loaded autophagy receptors to facilitate engulfment,
    sometimes mediated or supported by additional adaptor proteins.

  • The view that proteins act as single entities has been replaced with the concept suggesting that dynamic reorganization of multimeric soluble complexes annotated as signalosomes
    is essential for signal transmission in the cell.

  • [50] Complexes involved in tumorigenesis were studied by several CEF groups, including the leukemogenic AF4-MLL fusion protein[51] and RIP1-containing cytosolic complexes
    that are critical for the initiation and fine-tuning of different forms of cell death, i.e.

  • [57] The mechanism of membrane insertion of tail-anchored proteins was studied by structural and biochemical characterization of the interaction of the soluble Get3 protein
    with the cytoplasmatic domains of the membrane-bound receptors Get1 and Get2.

  • Additional foci of CEF research were genetic quality control in oocytes and epithelial stem cells by the p53 protein and the regulation of and by kinases.

  • Regulation of the activity of these complexes is achieved by their dynamic composition as well as by post-translational modifications (PTMs) of proteins.

  • [75][76] Another study, in collaboration with Edinburg University, analysed the RNA helicase Prp43 by crosslinking of RNA and analysis of cDNA (and provided first insights
    into the functional roles of this enzyme in ribosome biogenesis[77] CEF scientists also identified plant-specific ribosome biogenesis factors in A. thaliana with essential function in rRNA processing[78] and showed that the 60S-associated
    ribosome biogenesis factor LSG1-2 is required for 40S maturation in A.

  • Research into autophagy[edit] During selective autophagy, cargo is specifically targeted for degradation, and distinct cargo receptors have been described that regulate selectivity.

  • [84] Local maturation of the miRNA was found to be associated with a local reduction in protein synthesis, showing that localized miRNA maturation can modulate target gene
    expression with local and temporal precision.

  • CEF scientists evaluated members of the SR protein family for their potential to act as adaptors for nuclear export factor 1 (NXF1) and thereby couple pre-mRNA processing
    to mRNA export.

  • Structural description of RNA elements and their dynamics[edit] The combination of high-resolution NMR-based analysis of RNA structures[59][60] and time-resolved ligand-induced
    refolding of RNAs by caging distinct conformations[61] together with pulsed electron paramagnetic resonance methods after base-specific spin-labeling[62][63][64] and ultrafast laser spectroscopy of RNA dynamics[65][66] has led to the description
    of the structural dynamics of several RNAs.

  • CEF scientists have developed bromodomain inhibitors that can be used to study the function of these acetyl-lysine modification binding domains.

  • [35] CEF scientists also revealed the molecular mechanism of a novel type of phosphoribosyl-linked serine ubiquitination by the effector SdeA of the pathogen Legionella, which
    is very different from the canonical lysine-based ubiquitination mechanism.

  • CEF scientists also showed that for the guanine-sensing xpt-pbuX riboswitch of B. subtilis, the conformation of the full-length transcripts is static: it exclusively populates
    the functional off-state but cannot switch to the on-state, regardless of the presence or absence of ligand.

  • [79] Distribution of RNA-modifying enzymes and RNA molecules[edit] The dynamics of RNPs in native environments in eukaryotic cells were visualized and quantified using high-resolution
    microscopy.

  • They further discovered that reticulon-type proteins act as ER-specific autophagy receptors and simulated their effect on the membrane curvature.

  • [82] They found that >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo.

  • CEF Research Area B – Composition and dynamics of macromolecular complexes in quality control and signalling[edit] The characterization of function and structural composition
    of signalling complexes controlling cellular quality control programs was one of the major topics of CEF research.

  • [130] New building principles for DNA-nanoarchitectures have been established in CEF Also, new RNA riboswitches have been designed that can be triggered with small metabolites,
    exogenous molecules, or by temperature changes, as well as aptamers or self-cleaving ribozymes, which can be used to control gene expression in vivo.

  • [134] Making macromolecules further accessible on the nano-scale for manipulation, CEF developed generally applicable methods to organize macromolecular complexes in two dimensions
    with very high precision, as well as small synthetic gatekeepers and novel “light switches” to control biomolecular interactions and assembly of macromolecular complexes An approach to assemble three-dimensional protein networks by two-photon
    activation was developed.

  • CEF Research Area D – Design of macromolecular complexes[edit] A major focus of work in CEF was to develop and use methods and to explore proteins that enable modulating cellular
    and molecular function with light.

  • They also developed an approach for the chemo‐enzymatic synthesis of position‐specifically modified RNA for biophysical studies including light control.

  • [103] They also generated several mutant ChR2 versions with altered ion conductance (for example increased Ca2+-permeability in “CatCh”, a Ca2+ transporting channelrhodopsin)
    or kinetics, representing highly useful additions to the optogenetic toolbox .

  • [127] They also developed a minimal light‐switchable module enabling the formation of an intermolecular and conformationally well‐defined DNA G‐quadruplex structure with a
    photoswitchable azobenzene residue as part of the backbone structure.

  • A rational and minimally invasive protein engineering approach was used that left the molecular mechanisms of FASs unchanged and identified five mutations that can make baker’s
    yeast produce short-chain fatty acids.

  • [129] Using light-inducible antimiRs, CEF scientists also investigated if locally restricted target miRNA activity has a therapeutic benefit in diabetic wound healing and
    found that light can be used to locally activate therapeutically active antimiRs in vivo.

  • The study showed that DNP-enhanced solid-state NMR is a key method for bridging the gap between X-ray–based structure analysis and functional studies towards a highly resolved
    molecular picture .

  • Optochemical approaches, in contrast, use chemically engineered molecules to achieve light-effects in biological tissue.

  • [123][124] Wavelength-selective light-triggering was established for nucleic acids[125] as well as three-dimensional control of DNA hybridization by orthogonal two-colour
    two-photon uncaging.

  • CEF scientists together with colleagues from other German universities developed a novel approach to alter the functional properties of rhodopsin optogenetic tools, namely
    by modifications of the retinal chromophore.

  • [122] Furthermore, light-activatable interaction of DNA nanoarchitectures, light-dependent conformational changes in nucleic acids, light-dependent RNA interference and light-dependent
    transcription were realized.

  • [113] CEF scientists have also used optogenetic tools for the analysis of neural circuits and how they drive behaviour.

  • [161][162] Other novel light microscopy techniques used by CEF scientists include techniques that provide single-molecule sensitivity and a spatial resolution below the diffraction
    limit to study the structural organization of biomolecules in cells.

  • Software tools developed by CEF scientists include for example SuReSim, a software developed in collaboration with Heidelberg University, that simulates localization data
    of arbitrary three-dimensional structures represented by ground truth models, allowing users to systematically explore how changing experimental parameters can affect potential imaging outcomes.

  • This work was the first NMR study of a eukaryotic transporter protein complex and demonstrated the power of solid-state NMR in this field[170] They also demonstrated the power
    of DNP-enhanced solid-state NMR to bridge the gap between functional and structural data and models.

  • CEF Research Area E – Methods for studying macromolecular complexes[edit] The development of cutting-edge methodologies, including electron paramagnetic resonance, time-resolved
    nuclear magnetic resonance spectroscopy, advanced fluorescence microscopy, as well as optogenetics and optochemical biology has been instrumental in the research efforts of CEF.

  • Studies included molecular systems like optical switches, natural and non-natural photosynthetic model systems and membrane protein complexes.

  • The study also demonstrated for the first-time the feasibility to resolve equilibrium populations at multiple domains and their interdependence for global conformational changes
    in a large membrane protein complex.

  • Spectroscopy methods[edit] A wide range of spectroscopy methods for biological applications were available within CEF and CEF scientists have made significant progress in
    further developing biomolecular NMR and EPR.

  • [166][167] Collectively, the new tools provide additional avenues to specifically manipulate and trap cellular proteins, and, at the same time, for high-resolution read-out
    by single-molecule based microscopy.

  • [165] The close collaborative teamwork of the consortium allowed tackling two major challenges in live-cell as well as single-molecule localization microscopy: efficient delivery
    of fluorophores across cell membranes and high-density protein tracing by ultra small labels.

  • By investing in this new technology, CEF members have been able to speed up structure determination and also solve the structures of macromolecular complexes that were not
    amenable to x-ray crystallography studies.

  • [157] CEF scientists used LSFM, for example, to image in detail the complete embryonic development of different evolutionary unrelated insects and to establish the rules and
    self-organizing properties of post-embryonic plant organ cell division patterns.

  • This is an essential prerequisite to allow conclusions about the solution state protein complex, based on the gas phase measurements.

  • This method enables the observation of extremely fast chemical and biological reactions in real time involving a wide variety of molecules from small organic compounds to
    complex enzymes.

  • [172] PELDOR spectroscopy proved to be a versatile tool for structural investigations of proteins, even in the cellular environment.

  • Information-mining algorithms exploit structural data from various techniques, identify distinct macromolecules and computationally fit atomic resolution structures in the
    cellular tomograms, thereby bridging the resolution gap.

  • CEF contributed to the development of laser-induced liquid bead ion desorption mass spectrometry (LILBID), a method developed at Goethe University that is especially suited
    to the analysis of large membrane protein complexes.

  • CEF scientists used custom-tailored code and pipelines for fast and efficient analysis[191] of omics data, with a primary focus on protein-RNA interactions and posttranscriptional
    regulation.

  • Examples of these studies include the investigation and deciphering of the dynamics of photoswitchable or photolabile compounds as basis for the design of photoresponsive
    biomacromolecules, of the primary reaction dynamics of channelrhodopsin-2 (ChR2) and of the conformational dynamics of antibiotic-binding aptamers: Photochromic spiropyrans are organic molecules that can be used for the triggering of biological
    reactions.

  • [174] A challenge in native mass spectrometry is maintaining the features of the proteins of interest, such as oligomeric state, bound ligands, or the conformation of the
    protein complex, during the transfer from the solution to the gas phase.

  • Because with LSFM biological specimens survive long-term three-dimensional imaging at high spatiotemporal resolution, such microscopes have become the tool of choice in developmental
    biology.

  • Advantages of mass spectrometry compared to other methods like X-ray crystallography or nuclear magnetic resonance are for instance its lower limits of detection, its speed
    and its capability to deal with heterogeneous samples.

  • Direct electron detectors, in the development of which the MPI of Biophysics was involved, have exceeded all expectations[152][153] With these detectors, images can be captured
    with much higher contrast than with the CCD cameras previously used and have led to amazing progress in structural biology.

  • [158][159][160] The large amount of data produced by advanced light microscopy has made automated image analysis a necessity and CEF has contributed to improved data processing
    and modelling of advanced light microscopy data.

  • [163] Using the newly developed techniques, CEF scientists were able to establish the role of the linear ubiquitin coat around the cytosolic pathogen Salmonella Typhimurium
    as the local NF-κB signalling platform and provided insights into the function of OTULIN in NF-κB activation during bacterial pathogenesis.

  • Bridging between fundamental physics, chemistry and biology, CEF scientists studied biomolecular processes over a broad resolution range, from quantum mechanics to chemical
    kinetics, from atomistic descriptions of physical processes and chemical reactions in molecular dynamics (MD) simulations to highly coarse-grained models of the non-equilibrium operation of molecular machines and network descriptions of protein
    interactions.

  • Such tomograms contain a large amount of information as they are essentially a three-dimensional map of the cellular proteome and depict the whole network of macromolecular
    interactions.

  • Theoretical biophysics and bioinformatics[edit] Method development in theoretical biophysics plays an increasingly important role in the study of macromolecular complexes
    and has made essential contributions to many studies in the other research areas of CEF.

  • They also develops algorithms to solve problems in molecular biology, ranging from atomic protein structure analysis to computational systems biology.

  • Their goal is to develop detailed and quantitative descriptions of key biomolecular processes, including energy conversion, molecular transport, signal transduction, and enzymatic
    catalysis.

 

Works Cited

[‘”Method of the Year 2010″. Nature Methods. 8 (1): 1. 2010. doi:10.1038/nmeth.f.321.
2. ^ “Light-sheet fluorescence microscopy can image living samples in three dimensions with relatively low phototoxicity and at high speed”. Nature Methods. 12 (1):
1. 2014. doi:10.1038/nmeth.3251. PMID 25699311.
3. ^ Hunte C, Zickermann V, Brandt U (2010). “Functional modules and structural basis of conformational coupling in mitochondrial complex I”. Science. 329 (5990): 448–51. Bibcode:2010Sci…329..448H.
doi:10.1126/science.1191046. PMID 20595580. S2CID 11159551.
4. ^ Zickermann V, Wirth C, Nasiri H, Siegmund K, Schwalbe H, Hunte C, Brandt U (2015). “Mechanistic insight from the crystal structure of mitochondrial complex I”. Science. 347 (6217):
44–49. Bibcode:2015Sci…347…44Z. doi:10.1126/science.1259859. PMID 25554780. S2CID 23582849.
5. ^ Hahn A, Parey K, Bublitz M, Mills Deryck J, Zickermann V, Vonck J, Kühlbrandt W, Meier T (2016). “Structure of a complete ATP synthase dimer reveals
the molecular basis of inner mitochondrial membrane morphology”. Mol Cell. 63 (3): 445–56. doi:10.1016/j.molcel.2016.05.037. PMC 4980432. PMID 27373333.
6. ^ Mühleip AW, Joos F, Wigge C, Frangakis AS, Kühlbrandt W, Davies KM (2016). “Helical arrays
of U-shaped ATP synthase dimers form tubular cristae in ciliate mitochondria”. Proc Natl Acad Sci USA. 113 (30): 8442–8447. Bibcode:2016PNAS..113.8442M. doi:10.1073/pnas.1525430113. PMC 4968746. PMID 27402755.
7. ^ Murphy BJ, Klusch N, Langer J,
Mills DJ, Yildiz O, Kühlbrandt W (2019). “Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F1-Fo coupling”. Science. 364 (6446): eaaw9128. Bibcode:2019Sci…364.9128M. doi:10.1126/science.aaw9128. PMID 31221832. S2CID 195188479.
8. ^
Hahn A, Vonck J, Mills DJ, Meier T, Kühlbrandt W (2018). “Structure, mechanism, and regulation of the chloroplast ATP synthase”. Science. 360 (6389): 620. doi:10.1126/science.aat4318. PMC 7116070. PMID 29748256.
9. ^ Davies KM, Strauss M, Daum B,
Kief JH, Osiewacz HD, Rycovska A, Zickermann V, Kühlbrandt W (2011). “Macromolecular organization of ATP synthase and complex I in whole mitochondria”. Proc Natl Acad Sci USA. 108 (34): 14121–14126. Bibcode:2011PNAS..10814121D. doi:10.1073/pnas.1103621108.
PMC 3161574. PMID 21836051.
10. ^ Davies KM, Blum TB, Kühlbrandt W (2018). “Conserved in situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants”. Proc Natl Acad Sci USA. 115 (12): 3024–3029.
Bibcode:2018PNAS..115.3024D. doi:10.1073/pnas.1720702115. PMC 5866595. PMID 29519876.
11. ^ Buschmann S, Warkentin E, Xie H, Langer JD, Ermler U, Michel H (2010). “The structure of cbb3 cytochrome oxidase provides insights into proton pumping”.
Science. 329 (5989): 327–329. Bibcode:2010Sci…329..327B. doi:10.1126/science.1187303. PMID 20576851. S2CID 5083670.
12. ^ Safarian S, Rajendran C, Müller H, Preu J, Langer JD, Ovchinnikov S, Hirose T, Kusumoto T, Sakamoto J, Michel H (2016). “Structure
of a bd oxidase indicates similar mechanisms for membrane-integrated oxygen reductases”. Science. 352 (6285): 583–586. Bibcode:2016Sci…352..583S. doi:10.1126/science.aaf2477. PMC 5515584. PMID 27126043.
13. ^ Marcia M, Ermler U, Peng GH, Michel
H (2009). “The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration”. Proc Natl Acad Sci USA. 106 (24): 9625–9630. Bibcode:2009PNAS..106.9625M. doi:10.1073/pnas.0904165106. PMC
2689314. PMID 19487671.
14. ^ Bausewein T, Mills DJ, Langer JD, Nitschke B, Nussberger S, Kühlbrandt W (2017). “Cryo-EM structure of the TOM core complex from Neurospora crassa”. Cell. 170 (4): 693–700.e7. doi:10.1016/j.cell.2017.07.012. PMID 28802041.
15. ^
Diskowski M, Mehdipour AR, Wunnicke D, Mills DJ, Mikusevic V, Bärland N, Hoffmann J, Morgner N, Steinhoff HJ, Hummer G, Vonck J, Hänelt I (2017). “Helical jackknives control the gates of the double-pore K+ uptake system KtrAB”. eLife. 6: e24303. doi:10.7554/eLife.24303.
PMC 5449183. PMID 28504641.
16. ^ Schulze S, Koster S, Geldmacher U, Terwisscha van Scheltinga AC, Kühlbrandt W (2010). “Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT” (PDF). Nature. 467 (7312): 233–6. Bibcode:2010Natur.467..233S.
doi:10.1038/nature09310. PMID 20829798. S2CID 4341977.
17. ^ Ressl S, Terwisscha van Scheltinga AC, Vonrhein C, Ott V, Ziegler C (2009). “Molecular basis of transport and regulation in the Na+/betaine symporter BetP” (PDF). Nature. 458 (7234): 47–52.
Bibcode:2009Natur.458…47R. doi:10.1038/nature07819. PMID 19262666. S2CID 205216142.
18. ^ Eicher T, Seeger MA, Anselmi C, Zhou W, Brandstätter L, Verrey F, Diederichs K, Faraldo-Gómez JD, Pos KM (2014). “Coupling of remote alternating-access transport
mechanisms for protons and substrates in the multidrug efflux pump AcrB”. eLife. 3: e03145. doi:10.7554/eLife.03145.001. PMC 4359379. PMID 25248080.
19. ^ Eicher T, Cha HJ, Seeger MA, Brandstatter L, El-Delik J, Bohnert JA, Kern WV, Verrey F, Grutter
MG, Diederichs K, Pos KM (2012). “Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop”. Proc Natl Acad Sci USA. 109 (15): 5687–92. Bibcode:2012PNAS..109.5687E. doi:10.1073/pnas.1114944109.
PMC 3326505. PMID 22451937.
20. ^ Thomas C, Tampé R (2017). “Structure of the TAPBPR–MHC I complex defines the mechanism of peptide loading and editing”. Science. 358 (6366): 1060–1064. Bibcode:2017Sci…358.1060T. doi:10.1126/science.aao6001. PMID
29025996.
21. ^ Blees A, Januliene D, Hofmann T, Koller N, Schmidt C, Trowitzsch S, Moeller A, Tampé R (2017). “Structure of the human MHC-I peptide-loading complex”. Nature. 551 (7681): 525–528. Bibcode:2017Natur.551..525B. doi:10.1038/nature24627.
PMID 29107940. S2CID 4447406.
22. ^ Lehnert E, Mao J, Mehdipour AR, Hummer G, Abele R, Glaubitz C, Tampé R (2016). “Antigenic peptide recognition on the human ABC transporter TAP resolved by DNP-enhanced solid-state NMR spectroscopy”. J Am Chem
Soc. 138 (42): 13967–13974. doi:10.1021/jacs.6b07426. PMID 27659210.
23. ^ Barth K, Hank S, Spindler PE, Prisner TF, Tampé R, Joseph B (2018). “Conformational coupling and trans-inhibition in the human antigen transporter ortholog TmrAB resolved
with dipolar EPR spectroscopy”. J Am Chem Soc. 140 (13): 4527–4533. doi:10.1021/jacs.7b12409. PMID 29308886.
24. ^ Kaur H, Lakatos-Karoly A, Vogel R, Nöll A, Tampé R, Glaubitz C (2016). “Coupled ATPase-adenylate kinase activity in ABC transporters”.
Nat Commun. 7: 13864. Bibcode:2016NatCo…713864K. doi:10.1038/ncomms13864. PMC 5192220. PMID 28004795.
25. ^ Hellmich UA, Lyubenova S, Kaltenborn E, Doshi R, van Veen HW, Prisner TF, Glaubitz C (2012). “Probing the ATP hydrolysis cycle of the ABC
multidrug transporter LmrA by pulsed EPR spectroscopy”. J Am Chem Soc. 134 (13): 5857–62. doi:10.1021/ja211007t. PMID 22397466.
26. ^ Ong YS, Lakatos A, Becker-Baldus J, Pos KM, Glaubitz C (2013). “Detecting substrates bound to the secondary multidrug
efflux pump EmrE by DNP-enhanced solid-state NMR”. J Am Chem Soc. 135 (42): 15754–62. doi:10.1021/Ja402605s. PMID 24047229.
27. ^ Hempelmann F, Hölper S, Verhoefen MK, Woerner AC, Köhler T, Fiedler SA, Pfleger N, Wachtveitl J, Glaubitz C (2011).
“The His75-Asp97 cluster in green proteorhodopsin”. J Am Chem Soc. 133 (12): 4645–4654. doi:10.1021/ja111116a. PMID 21366243.
28. ^ Reckel S, Gottstein D, Stehle J, Löhr F, Verhoefen MK, Takeda M, Silvers R, Kainosho M, Glaubitz C, Wachtveitl J,
Bernhard F, Schwalbe H, Güntert P, Dötsch V (2011). “Solution NMR structure of proteorhodopsin”. Angewandte Chemie International Edition. 50 (50): 11942–11946. doi:10.1002/anie.201105648. PMC 4234116. PMID 22034093.
29. ^ Maciejko J, Kaur J, Becker-Baldus
J, Glaubitz C (2019). “Photocycle-dependent conformational changes in the proteorhodopsin cross-protomer Asp-His-Trp triad revealed by DNP-enhanced MAS-NMR”. Proc Natl Acad Sci USA. 116 (17): 8342–8349. Bibcode:2019PNAS..116.8342M. doi:10.1073/pnas.1817665116.
PMC 6486740. PMID 30948633.
30. ^ Morgner N, Kleinschroth T, Barth HD, Ludwig B, Brutschy B (2007). “A novel approach to analyze membrane proteins by laser mass spectrometry: From protein subunits to the integral complex”. J Am Soc Mass Spectrom.
18 (8): 1429–1438. doi:10.1016/j.jasms.2007.04.013. PMID 17544294.
31. ^ Joedicke L, Mao J, Kuenze G, Reinhart C, Kalavacherla T, Jonker HR, Richter C, Schwalbe H, Meiler J, Preu J, Michel H, Glaubitz C (2018). “The molecular basis of subtype selectivity
of human kinin G-protein-coupled receptors”. Nat Chem Biol. 14 (3): 284–290. doi:10.1038/nchembio.2551. PMC 7992120. PMID 29334381.
32. ^ Dikic I, Elazar Z (2018). “Mechanism and medical implications of mammalian autophagy”. Nat Rev Mol Cell Biol.
19 (6): 349–364. doi:10.1038/s41580-018-0003-4. PMID 29618831. S2CID 4594197.
33. ^ Genau HM, Huber J, Baschieri F, Akutsu M, Dötsch V, Farhan H, Rogov V, Behrends C (2015). “CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to
spatially restrict TIAM1-RAC1 signaling”. Mol Cell. 57 (6): 995–1010. doi:10.1016/j.molcel.2014.12.040. PMID 25684205.
34. ^ Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C, Dötsch V, Bumann
D, Dikic I (2011). “Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth”. Science. 333 (6039): 228–33. Bibcode:2011Sci…333..228W. doi:10.1126/science.1205405. PMC 3714538. PMID 21617041.
35. ^ Fiskin E, Bionda T, Dikic
I, Behrends C (2016). “Global analysis of host and bacterial ubiquitinome in response to Salmonella Typhimurium infection”. Mol Cell. 62 (6): 967–981. doi:10.1016/j.molcel.2016.04.015. PMID 27211868.
36. ^ Bhogaraju S, Kalayil S, Liu Y, Bonn F,
Colby T, Matic I, Dikic I (2016). “Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination”. Cell. 167 (6): 1636–1649.e13. doi:10.1016/j.cell.2016.11.019. PMID 27912065.
37. ^ Kalayil S, Bhogaraju
S, Bonn F, Shin D, Liu Y, Gan N, Basquin J, Grumati P, Luo ZQ, Dikic I (2018). “nsights into catalysis and function of phosphoribosyl-linked serine ubiquitination”. Nature. 557 (7707): 734–738. Bibcode:2018Natur.557..734K. doi:10.1038/s41586-018-0145-8.
PMC 5980784. PMID 29795347.
38. ^ Bhogaraju S, Bonn F, Mukherjee R, Adams M, Pfleiderer MM, Galej WP, Matkovic V, Lopez-Mosqueda J, Kalayil S, Shin D, Dikic I (2019). “Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin-catalysed glutamylation”.
Nature. 572 (7769): 382–386. Bibcode:2019Natur.572..382B. doi:10.1038/s41586-019-1440-8. PMC 6715450. PMID 31330532.
39. ^ Khaminets A, Heinrich T, Mari M, Grumati P, Huebner AK, Akutsu M, Liebmann L, Stolz A, Nietzsche S, Koch N, Mauthe M, Katona
I, Qualmann B, Weis J, Reggiori F, Kurth I, Hübner CA, Dikic I (2015). “Regulation of endoplasmic reticulum turnover by selective autophagy”. Nature. 522 (7556): 354–8. Bibcode:2015Natur.522..354K. doi:10.1038/nature14498. PMID 26040720. S2CID 4449106.
40. ^
Bhaskara RM, Grumati P, Garcia-Pardo J, Kalayil S, Covarrubias-Pinto A, Chen W, Kudryashev M, Dikic I, Hummer G (2019). “Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy”. Nat Commun. 10 (1):
2370. Bibcode:2019NatCo..10.2370B. doi:10.1038/s41467-019-10345-3. PMC 6542808. PMID 31147549.
41. ^ Husnjak K, Elsasser S, Zhang NX, Chen X, Randles L, Shi Y, Hofmann K, Walters KJ, Finley D, Dikic I (2008). “Proteasome subunit Rpn13 is a novel
ubiquitin receptor”. Nature. 453 (7194): 481–488. Bibcode:2008Natur.453..481H. doi:10.1038/nature06926. PMC 2839886. PMID 18497817.
42. ^ Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow
F, Wakatsuki S, Dikic I (2009). “Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation”. Cell. 136 (6): 1098–1109. doi:10.1016/j.cell.2009.03.007. PMID 19303852. S2CID 3683855.
43. ^ Ikeda F, Deribe YL, Skånland
SS, Stieglitz B, Grabbe C, Franz-Wachtel M, van Wijk SJ, Goswami P, Nagy V, Terzic J, Tokunaga F, Androulidaki A, Nakagawa T, Pasparakis M, Iwai K, Sundberg JP, Schaefer L, Rittinger K, Macek B, Dikic I (2011). “SHARPIN forms a linear ubiquitin ligase
complex regulating NF-kappa B activity and apoptosis”. Nature. 471 (7340): 637–641. Bibcode:2011Natur.471..637I. doi:10.1038/nature09814. PMC 3085511. PMID 21455181.
44. ^ von Delbrück M, Kniss A, Rogov VV, Pluska L, Bagola K, Löhr F, Güntert P,
Sommer T, Dötsch V (2016). “The CUE domain of Cue1 aligns growing ubiquitin chains with Ubc7 for rapid elongation”. Mol Cell. 62 (6): 918–928. doi:10.1016/j.molcel.2016.04.031. PMID 27264873.
45. ^ van Wijk SJ, Fricke F, Herhaus L, Gupta J, Hötte
K, Pampaloni F, Grumati P, Kaulich M, Sou YS, Komatsu M, Greten FR, Fulda S, Heilemann M, Dikic I (2017). “Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation”. Nat Microbiol. 2 (7): 17066.
doi:10.1038/nmicrobiol.2017.66. PMID 28481361. S2CID 1329736.
46. ^ Kniss A, Schuetz D, Kazemi S, Pluska L, Spindler PE, Rogov VV, Husnjak K, Dikic I, Güntert P, Sommer T, Prisner TF, Dötsch V (2018). “Chain assembly and disassembly processes differently
affect the conformational space of ubiquitin chains”. Structure. 26 (2): 249–258.e4. doi:10.1016/j.str.2017.12.011. PMID 29358025.
47. ^ Deutsch GB, Zielonka EM, Coutandin D, Weber TA, Schäfer B, Hannewald J, Luh LM, Durst FG, Ibrahim M, Hoffmann
J, Niesen FH, Sentürk A, Kunkel H, Brutschy B, Schleiff E, Knapp S, Acker-Palmer A, Grez M, McKeon F, Dötsch V (2011). “DNA damage in oocytes induces a switch of the quality control factor TAp63a from dimer to tetramer”. Cell. 144 (4): 566–576. doi:10.1016/j.cell.2011.01.013.
PMC 3087504. PMID 21335238.
48. ^ Coutandin D, Osterburg C, Srivastav RK, Sumyk M, Kehrloesser S, Gebel J, Tuppi M, Hannewald J, Schafer B, Salah E, Mathea S, Müller-Kuller U, Doutch J, Grez M, Knapp S, Dötsch V (2016). “Quality control in oocytes
by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level”. eLife. 5: e13909. doi:10.7554/eLife.13909. PMC 4876613. PMID 27021569.
49. ^ Tuppi M, Kehrloesser S, Coutandin DW, Rossi V, Luh LM, Strubel A, Hötte K,
Hoffmeister M, Schäfer B, De Oliveira T, Greten F, Stelzer EH, Knapp S, De Felici M, Behrends C, Klinger FG, Dötsch V (2018). “Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63”. Nat Struct Mol Biol.
25 (3): 261–269. doi:10.1038/s41594-018-0035-7. PMID 29483652. S2CID 3685994.
50. ^ Russo C, Osterburg C, Sirico A, Antonini D, Ambrosio R, Würz JM, Rinnenthal J, Ferniani M, Kehrloesser S, Schäfer B, Güntert P, Sinha S, Dötsch V, Missero (2018).
“Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome”. Proc Natl Acad Sci USA. 115 (5): E906–E915. Bibcode:2018PNAS..115E.906R. doi:10.1073/pnas.1713773115. PMC 5798343. PMID 29339502.
51. ^ Benedikt
A, Baltruschat S, Scholz B, Bursen A, Arrey TN, Meyer B, Varagnolo L, Müller AM, Karas M, Dingermann T, Marschalek R (2011). “The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures”. Leukemia. 25
(1): 135–44. doi:10.1038/leu.2010.249. PMID 21030982.
52. ^ Schmidt N, Kowald L, Wijk S, Fulda S (2019). “Differential involvement of TAK1, RIPK1 and NF-kappaB signaling in Smac mimetic-induced cell death in breast cancer cells”. Biol Chem. 400
(2): 171–180. doi:10.1515/hsz-2018-0324. PMID 30391931. S2CID 53241442.
53. ^ Belz K, Schoeneberger H, Wehner S, Weigert A, Bonig H, Klingebiel T, Fichtner I, Fulda S (2014). “Smac mimetic and glucocorticoids synergize to induce apoptosis in childhood
ALL by promoting ripoptosome assembly”. Blood. 124 (2): 240–50. doi:10.1182/blood-2013-05-500918. PMID 24855207.
54. ^ Müller S; Ackloo S; Arrowsmith CH; Bauser M; Baryza JL; Blagg J; Böttcher J; Bountra C; Brown PJ; Bunnage ME; Carter AJ; Damerell
D; Dötsch V; Drewry DH; Edwards AM; Edwards J; Elkins JM; Fischer C; Frye SV; Gollner A; Grimshaw CE; Ijzerman A; Hanke T; Hartung IV; Hitchcock S; Howe T; Hughes TV; Laufer S; Li VMJ; Liras S; Marsden BD; Matsui H; Mathias J; O’Hagan RC; Owen DR;
Pande V; Rauh D; Rosenberg SH; Roth BL; Schneider NS; Scholten C; Singh Saikatendu K; Simeonov A; Takizawa M; Tse C; Thompson PR; Treiber DK; Viana AYI; Wells CI; Willson TM; Zuercher WJ; Knapp S; Mueller-Fahrnow A (2018). “Donated chemical probes
for open science”. eLife. 7: e34311. doi:10.7554/eLife.34311. PMC 5910019. PMID 29676732.
55. ^ Wu Q, Heidenreich D, Zhou S, Ackloo S, Krämer A, Nakka K, Lima-Fernandes E, Deblois G, Duan S, Vellanki RN, Li F, Vedadi M, Dilworth J, Lupien M, Brennan
PE, Arrowsmith CH, Müller S, Fedorov O, Filippakopoulos P, Knapp S (2019). “A chemical toolbox for the study of bromodomains and epigenetic signaling”. Nat Commun. 10 (10: 1915): 1915. Bibcode:2019NatCo..10.1915W. doi:10.1038/s41467-019-09672-2. PMC
6478789. PMID 31015424.
56. ^ Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, Acker-Palmer A (2010). “Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis”. Nature. 465 (7297): 487–91. Bibcode:2010Natur.465..487S.
doi:10.1038/nature08995. PMID 20445540. S2CID 4423684.
57. ^ Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, Klein R, Acker-Palmer A (2008). “Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors”. Nat
Neurosci. 11 (9): 1035–1043. doi:10.1038/nn.2171. PMID 19160501. S2CID 698572.
58. ^ Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Löhr F, Bernhard F, Denic V, Dötsch V, Sinning I (2011). “Structural basis for tail-anchored
membrane protein biogenesis by the Get3-receptor complex”. Science. 333 (6043): 758–62. Bibcode:2011Sci…333..758S. doi:10.1126/science.1207125. PMC 3601824. PMID 21719644.
59. ^ Cherepanov AV, Glaubitz C, Schwalbe H (2010). “High-resolution studies
of uniformly 13C,15N-labeled RNA by solid-state NMR spectroscopy”. Angewandte Chemie International Edition. 49 (28): 4747–50. doi:10.1002/anie.200906885. PMID 20533472.
60. ^ Schnieders R, Wolter AC, Richter C, Wöhnert J, Schwalbe H, Fürtig B (2019).
“Novel (13) C-detected NMR experiments for the precise detection of RNA structure”. Angewandte Chemie International Edition. 58 (27): 9140–9144. doi:10.1002/anie.201904057. PMC 6617721. PMID 31131949.
61. ^ Buck J, Fürtig B, Noeske J, Wöhnert J,
Schwalbe H (2007). “Time-resolved NMR methods resolving ligand-induced RNA folding at atomic resolution”. Proc Natl Acad Sci USA. 104 (40): 15699–704. Bibcode:2007PNAS..10415699B. doi:10.1073/pnas.0703182104. PMC 2000436. PMID 17895388.
62. ^ Krstic
I, Frolow O, Sezer D, Endeward B, Weigand JE, Suess B, Engels JW, Prisner TF (2010). “PELDOR spectroscopy reveals preorganization of the neomycin-responsive riboswitch tertiary structure”. J Am Chem Soc. 132 (5): 1454–5. doi:10.1021/ja9077914. PMID
20078041.
63. ^ Schiemann O, Piton N, Plackmeyer J, Bode BE, Prisner TF, Engels JW (2007). “Spin labeling of oligonucleotides with the nitroxide TPA and use of PELDOR, a pulse EPR method, to measure intramolecular distances”. Nat Protoc. 2 (4):
904–23. doi:10.1038/nprot.2007.97. PMID 17446891. S2CID 6442268.
64. ^ Weinrich T, Jaumann EA, Scheffer U, Prisner TF, Göbel MW (2018). “A cytidine phosphoramidite with protected nitroxide spin label: synthesis of a full-length TAR RNA and investigation
by in-line probing and EPR spectroscopy”. Chemistry: A European Journal. 24 (23): 6202–6207. doi:10.1002/chem.201800167. PMID 29485736.
65. ^ Förster U, Grunewald C, Engels JW, Wachtveitl J (2010). “Ultrafast dynamics of 1-ethynylpyrene-modified
RNA: a photophysical probe of intercalation”. J Phys Chem B. 114 (35): 11638–45. doi:10.1021/jp103176q. PMID 20707369.
66. ^ Gustmann H, Segler AJ, Gophane DB, Reuss AJ, Grünewald C, Braun M, Weigand JE, Sigurdsson ST, Wachtveitl J (2019). “Structure
guided fluorescence labeling reveals a two-step binding mechanism of neomycin to its RNA aptamer”. Nucleic Acids Res. 47 (1): 15–28. doi:10.1093/nar/gky1110. PMC 6326822. PMID 30462266.
67. ^ Reining A, Nozinovic S, Schlepckow K, Buhr F, Fürtig
B, Schwalbe H (2013). “Three-state mechanism couples ligand and temperature sensing in riboswitches”. Nature. 499 (7458): 355–9. Bibcode:2013Natur.499..355R. doi:10.1038/Nature12378. PMID 23842498. S2CID 4414719.
68. ^ Ferner J, Suhartono M, Breitung
S, Jonker HR, Hennig M, Wöhnert J, Gobel M, Schwalbe H (2009). “Structures of HIV TAR RNA-ligand complexes reveal higher binding stoichiometries”. ChemBioChem. 10 (9): 1490–1494. doi:10.1002/cbic.200900220. PMID 19444830. S2CID 44300779.
69. ^ Morgner
N, Barth HD, Brutschy B, Scheffer U, Breitung S, Gobel M (2008). “Binding sites of the viral RNA element TAR and of TAR mutants for various peptide ligands, probed with LILBID: A new laser mass spectrometry”. J Am Soc Mass Spectrom. 19 (11): 1600–1611.
doi:10.1016/j.jasms.2008.07.001. PMID 18693035.
70. ^ Manoharan V, Fürtig B, Jaschke A, Schwalbe H (2009). “Metal-induced folding of diels-alderase ribozymes studied by static and time-resolved NMR spectroscopy”. J Am Chem Soc. 131 (17): 6261–6270.
doi:10.1021/ja900244x. PMID 19354210.
71. ^ Kortmann J, Sczodrok S, Rinnenthal J, Schwalbe H, Narberhaus F (2011). “Translation on demand by a simple RNA-based thermosensor”. Nucleic Acids Res. 39 (7): 2855–2868. doi:10.1093/nar/gkq1252. PMC 3074152.
PMID 21131278.
72. ^ Duchardt-Ferner E, Weigand JE, Ohlenschlager O, Schtnidtke SR, Suess B, Wöhnert J (2010). “Highly modular structure and ligand binding by conformational capture in a minimalistic riboswitch”. Angewandte Chemie International
Edition. 49 (35): 6216–6219. doi:10.1002/anie.201001339. PMID 20632338.
73. ^ Steinert H, Sochor F, Wacker A, Buck J, Helmling C, Hiller F, Keyhani S, Noeske J, Grimm SK, Rudolph MM, Keller H, Mooney RA, Landick R, Suess B, Fürtig B, Wöhnert J,
Schwalbe H (2017). “Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation”. eLife. 6: e21297. doi:10.7554/eLife.21297. PMC 5459577. PMID 28541183.
74. ^ Neyer S, Kunz M, Geiss C, Hantsche
M, Hodirnau VV, Seybert A, Engel C, Scheffer MP, Cramer P, Frangakis AS (2016). “Structure of RNA polymerase I transcribing ribosomal DNA genes”. Nature. 540 (7634): 607–610. Bibcode:2016Natur.540..607N. doi:10.1038/nature20561. PMID 27842382. S2CID
205252425.
75. ^ Meyer B, Wurm JP, Kotter P, Leisegang MS, Schilling V, Buchhaupt M, Held M, Bahr U, Karas M, Heckel A, Bohnsack MT, Wöhnert J, Entian KD (2011). “The Bowen-Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome
biogenesis, as an essential assembly factor and in the methylation of Psi 1191 in yeast 18S rRNA”. Nucleic Acids Res. 39 (4): 1526–37. doi:10.1093/nar/gkq931. PMC 3045603. PMID 20972225.
76. ^ Wurm JP, Meyer B, Bahr U, Held M, Frolow O, Kotter P,
Engels JW, Heckel A, Karas M, Entian KD, Wöhnert J (2010). “The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N1-specific methyltransferase”. Nucleic Acids Res. 38 (7): 2387–98. doi:10.1093/nar/gkp1189. PMC
2853112. PMID 20047967.
77. ^ Bohnsack MT, Martin R, Granneman S, Ruprecht M, Schleiff E, Tollervey D (2009). “Prp43 bound at different sites on the pre-rRNA performs distinct functions in ribosome synthesis”. Mol Cell. 36 (4): 583–92. doi:10.1016/j.molcel.2009.09.039.
PMC 2806949. PMID 19941819.
78. ^ Palm D, Streit D, Shanmugam T, Weis BL, Ruprecht M, Simm S, Schleiff E (2019). “Plant-specific ribosome biogenesis factors in Arabidopsis thaliana with essential function in rRNA processing”. Nucleic Acids Res.
47 (4): 1880–1895. doi:10.1093/nar/gky1261. PMC 6393314. PMID 30576513.
79. ^ Weis BL, Missbach S, Marzi J, Bohnsack MT, Schleiff E (2014). “The 60S associated ribosome biogenesis factor LSG1-2 is required for 40S maturation in Arabidopsis thaliana”.
Plant J. 80 (6): 1043–56. doi:10.1111/tpj.12703. PMID 25319368.
80. ^ Endesfelder U, Finan K, Holden SJ, Cook PR, Kapanidis AN, Heilemann M (2013). “Multiscale spatial organization of RNA polymerase in Escherichia coli”. Biophys J. 105 (1): 172–181.
Bibcode:2013BpJ…105..172E. doi:10.1016/j.bpj.2013.05.048. PMC 3699759. PMID 23823236.
81. ^ Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jae N, Rossbach O, Amrhein C, Sigala F, Boon RA, Furtig B, Manavski Y, You
X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S (2016). “Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling
HuR-mediated post-transcriptional regulation”. Nat Med. 22 (10): 1140–1150. doi:10.1038/nm.4172. PMID 27595325. S2CID 3397638.
82. ^ Müller-McNicoll M, Botti V, Domingues AM, Brandl H, Schwich OD, Steiner MC, Curk T, Poser I, Zarnack K, Neugebauer
KM (2016). “SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export”. Genes Dev. 30 (5): 553–66. doi:10.1101/gad.276477.115. PMC 4782049. PMID 26944680.
83. ^ Braun S, Enculescu M, Setty ST, Cortes-Lopez M, de Almeida BP,
Sutandy FX, Schulz L, Busch A, Seiler M, Ebersberger S, Barbosa-Morais NL, Legewie S, König J, Zarnack K (2018). “Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis”. Nat Commun. 9 (1): 3315. Bibcode:2018NatCo…9.3315B.
doi:10.1038/s41467-018-05748-7. PMC 6098099. PMID 30120239.
84. ^ Sambandan S, Akbalik G, Kochen L, Rinne J, Kahlstatt J, Glock C, Tushev G, Alvarez-Castelao B, Heckel A, Schuman EM (2017). “Activity-dependent spatially localized miRNA maturation
in neuronal dendrites”. Science. 355 (6325): 634–637. Bibcode:2017Sci…355..634S. doi:10.1126/science.aaf8995. PMID 28183980. S2CID 17159252.
85. ^ Boon RA, Hofmann P, Michalik KM, Lozano-Vidal N, Berghauser D, Fischer A, Knau A, Jae N, Schurmann
C, Dimmeler S (2016). “Long noncoding RNA Meg3 controls endothelial cell aging and function implications for regenerative angiogenesis”. J Am Coll Cardiol. 68 (23): 2589–2591. doi:10.1016/j.jacc.2016.09.949. PMID 27931619.
86. ^ Michalik KM, You
X, Manavski Y, Doddaballapur A, Zörnig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, Boon RA, Dimmeler S (2014). “Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth”. Circ Res. 114 (9): 1389–1397. doi:10.1161/circresaha.114.303265.
PMID 24602777.
87. ^ Cremer S, Michalik KM, Fischer A, Pfisterer L, Jaé N, Winter C, Boon RA, Muhly-Reinholz M, John D, Uchida S, Weber C, Poller W, Günther S, Braun T, Li DY, Maegdefessel L, Matic Perisic L, Hedin U, Soehnlein O, Zeiher A, Dimmeler
S (2019). “Hematopoietic deficiency of the long non-coding RNA MALAT1 promotes atherosclerosis and plaque inflammation”. Circulation. 139 (10): 1320–1334. doi:10.1161/circulationaha.117.029015. PMID 30586743. S2CID 58561771.
88. ^ Nagel G, Szellas
T, Huhn W, Kateriya S, Adeishvili N, Berthold P, Ollig D, Hegemann P, Bamberg E (2003). “Channelrhodopsin-2, a directly light-gated cation-selective membrane channel”. Proc Natl Acad Sci USA. 100 (24): 13940–5. Bibcode:2003PNAS..10013940N. doi:10.1073/pnas.1936192100.
PMC 283525. PMID 14615590.
89. ^ Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005). “Millisecond-timescale, genetically targeted optical control of neural activity”. Nat Neurosci. 8 (9): 1263–1268. doi:10.1038/nn1525. PMID 16116447. S2CID
6809511.
90. ^ Feldbauer K, Zimmermann D, Pintschovius V, Spitz J, Bamann C, Bamberg E (2009). “Channelrhodopsin-2 is a leaky proton pump”. Proc Natl Acad Sci USA. 106 (30): 12317–12322. Bibcode:2009PNAS..10612317F. doi:10.1073/pnas.0905852106.
PMC 2718366. PMID 19590013.
91. ^ Lorenz-Fonfria VA, Resler T, Krause N, Nack M, Gossing M, Fischer von Mollard G, Bamann C, Bamberg E, Schlesinger R, Heberle J (2013). “Transient protonation changes in channelrhodopsin-2 and their relevance to
channel gating”. Proc Natl Acad Sci USA. 110 (14): E1273-81. Bibcode:2013PNAS..110E1273L. doi:10.1073/pnas.1219502110. PMC 3619329. PMID 23509282.
92. ^ Neumann-Verhoefen MK, Neumann K, Bamann C, Radu I, Heberle J, Bamberg E, Wachtveitl J (2013).
“Ultrafast infrared spectroscopy on channelrhodopsin-2 reveals efficient energy transfer from the retinal chromophore to the protein”. J Am Chem Soc. 135 (18): 6968–6976. doi:10.1021/Ja400554y. PMID 23537405.
93. ^ Kleinlogel S, Terpitz U, Legrum
B, Gokbuget D, Boyden ES, Bamann C, Wood PG, Bamberg E (2011). “A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins”. Nat Methods. 8 (12): 1083–1088. doi:10.1038/nmeth.1766. PMID 22056675. S2CID 11567708.
94. ^
Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A, Deisseroth K (2007). “Multimodal fast optical interrogation of neural circuitry”. Nature. 446 (7136): 633–9. Bibcode:2007Natur.446..633Z. doi:10.1038/nature05744.
PMID 17410168. S2CID 4415339.
95. ^ Oranth A, Schultheis C, Tolstenkov O, Erbguth K, Nagpal J, Hain D, Brauner M, Wabnig S, Steuer Costa W, McWhirter RD, Zels S, Palumbos S, Miller Iii DM, Beets I, Gottschalk A (2018). “Food sensation modulates
locomotion by dopamine and neuropeptide signaling in a distributed neuronal network”. Neuron. 100 (6): 1414–1428. doi:10.1016/j.neuron.2018.10.024. PMID 30392795.
96. ^ Stirman JN, Crane MM, Husson SJ, Wabnig S, Schultheis C, Gottschalk A, Lu H
(2011). “Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans”. Nat Methods. 8 (2): 153–8. doi:10.1038/nmeth.1555. PMC 3189501. PMID 21240278.
97. ^ Liewald JF, Brauner M, Stephens GJ, Bouhours M,
Schultheis C, Zhen M, Gottschalk A (2008). “Optogenetic analysis of synaptic function”. Nat Methods. 5 (10): 895–902. doi:10.1038/nmeth.1252. PMID 18794862. S2CID 17102550.
98. ^ Kittelmann M, Liewald JF, Hegermann J, Schultheiss C, Brauner M, Steuer
Costa W, Wabnig S, Eimer S, Gottschalk A (2013). “In vivo synaptic recovery following optogenetic hyperstimulation”. Proc Natl Acad Sci USA. 110 (32): E3007-16. Bibcode:2013PNAS..110E3007K. doi:10.1073/pnas.1305679110. PMC 3740886. PMID 23878262.
99. ^
Azimi Hashemi N, Bergs AC, Schüler C, Scheiwe AR, Steuer Costa W, Bach M, Liewald JF, Gottschalk A (2019). “Rhodopsin-based voltage imaging tools for use in muscles and neurons of Caenorhabditis elegans”. Proc Natl Acad Sci USA. 116 (34): 17051–17060.
Bibcode:2019PNAS..11617051A. doi:10.1073/pnas.1902443116. PMC 6708366. PMID 31371514.
100. ^ AzimiHashemi N, Erbguth K, Vogt A, Riemensperger T, Rauch E, Woodmansee D, Nagpal J, Brauner M, Sheves M, Fiala A, Kattner L, Trauner D, Hegemann P, Gottschalk
A, Liewald JF (2014). “Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools”. Nat Commun. 5: 5810. Bibcode:2014NatCo…5.5810A. doi:10.1038/Ncomms6810. PMID 25503804.
101. ^ Gao SQ,
Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A (2015). “Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp”. Nat Commun. 6: 8046. Bibcode:2015NatCo…6.8046G. doi:10.1038/ncomms9046.
PMC 4569695. PMID 26345128.
102. ^ Verhoefen MK, Bamann C, Blöcher R, Förster U, Bamberg E, Wachtveitl J (2010). “The photocycle of channelrhodopsin-2: ultrafast reaction dynamics and subsequent reaction steps”. ChemPhysChem. 11 (14): 3113–22. doi:10.1002/cphc.201000181.
PMID 20730849.
103. ^ Volkov O, Kovalev K, Polovinkin V, Borshchevskiy V, Bamann C, Astashkin R, Marin E, Popov A, Balandin T, Willbold D, Buldt G, Bamberg E, Gordeliy V (2017). “Structural insights into ion conduction by channelrhodopsin 2”. Science.
358 (6366): eaan8862. doi:10.1126/science.aan8862. PMID 29170206.
104. ^ Kleinlogel S, Feldbauer K, Dempski RE, Fotis H, Wood PG, Bamann C, Bamberg E (2011). “Ultra light-sensitive and fast neuronal activation with the Ca(2+)-permeable channelrhodopsin
CatCh” (PDF). Nat Neurosci. 14 (4): 513–8. doi:10.1038/nn.2776. PMID 21399632. S2CID 5907240.
105. ^ Becker-Baldus J, Bamann C, Saxena K, Gustmann H, Brown LJ, Brown RC, Reiter C, Bamberg E, Wachtveitl J, Schwalbe H, Glaubitz C (2015). “Enlightening
the photoactive site of channelrhodopsin-2 by DNP-enhanced solid-state NMR spectroscopy”. Proc Natl Acad Sci USA. 112 (32): 9896–901. Bibcode:2015PNAS..112.9896B. doi:10.1073/pnas.1507713112. PMC 4538646. PMID 26216996.
106. ^ Bamann C, Bamberg
E, Wachtveitl J, Glaubitz C (2014). “Proteorhodopsin”. Biochimica et Biophysica Acta (BBA) – Bioenergetics. Photo credit: https://www.flickr.com/photos/jamesxv7/7652532108/’]