Concerted transformation of a hyper-paused transcription complex and its reinforcing protein.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 Apr 2024
08 Apr 2024
Historique:
received:
22
08
2023
accepted:
28
03
2024
medline:
9
4
2024
pubmed:
9
4
2024
entrez:
8
4
2024
Statut:
epublish
Résumé
RfaH, a paralog of the universally conserved NusG, binds to RNA polymerases (RNAP) and ribosomes to activate expression of virulence genes. In free, autoinhibited RfaH, an α-helical KOW domain sequesters the RNAP-binding site. Upon recruitment to RNAP paused at an ops site, KOW is released and refolds into a β-barrel, which binds the ribosome. Here, we report structures of ops-paused transcription elongation complexes alone and bound to the autoinhibited and activated RfaH, which reveal swiveled, pre-translocated pause states stabilized by an ops hairpin in the non-template DNA. Autoinhibited RfaH binds and twists the ops hairpin, expanding the RNA:DNA hybrid to 11 base pairs and triggering the KOW release. Once activated, RfaH hyper-stabilizes the pause, which thus requires anti-backtracking factors for escape. Our results suggest that the entire RfaH cycle is solely determined by the ops and RfaH sequences and provide insights into mechanisms of recruitment and metamorphosis of NusG homologs across all life.
Identifiants
pubmed: 38589445
doi: 10.1038/s41467-024-47368-4
pii: 10.1038/s41467-024-47368-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3040Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : WA 1126/11-1, project number 433623608
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : INST 130/1064-1 FUGG
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : RO 617/21-1
Organisme : Academy of Finland (Suomen Akatemia)
ID : 341962
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : GM067153
Informations de copyright
© 2024. The Author(s).
Références
Werner, F. A nexus for gene expression-molecular mechanisms of Spt5 and NusG in the three domains of life. J. Mol. Biol. 417, 13–27 (2012).
pubmed: 22306403
pmcid: 3382729
doi: 10.1016/j.jmb.2012.01.031
Mayer, A. et al. Uniform transitions of the general RNA polymerase II transcription complex. Nat. Struct. Mol. Biol. 17, 1272–1278 (2010).
pubmed: 20818391
doi: 10.1038/nsmb.1903
Mooney, R. A. et al. Regulator trafficking on bacterial transcription units in vivo. Mol. Cell 33, 97–108 (2009).
pubmed: 19150431
pmcid: 2747249
doi: 10.1016/j.molcel.2008.12.021
Herbert, K. M. et al. E. coli NusG inhibits backtracking and accelerates pause-free transcription by promoting forward translocation of RNA polymerase. J. Mol. Biol. 399, 17–30 (2010).
pubmed: 20381500
pmcid: 2875378
doi: 10.1016/j.jmb.2010.03.051
Hirtreiter, A. et al. Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif. Nucleic Acids Res. 38, 4040–4051 (2010).
pubmed: 20197319
pmcid: 2896526
doi: 10.1093/nar/gkq135
Huang, Y. H. et al. Structure-based mechanisms of a molecular RNA polymerase/chaperone machine required for ribosome biosynthesis. Mol. Cell 79, 1024–1036.e1025 (2020).
pubmed: 32871103
doi: 10.1016/j.molcel.2020.08.010
Yakhnin, A. V. et al. Robust regulation of transcription pausing in Escherichia coli by the ubiquitous elongation factor NusG. Proc. Natl Acad. Sci. USA 120, e2221114120 (2023).
pubmed: 37276387
pmcid: 10268239
doi: 10.1073/pnas.2221114120
Bernecky, C., Plitzko, J. M. & Cramer, P. Structure of a transcribing RNA polymerase II-DSIF complex reveals a multidentate DNA-RNA clamp. Nat. Struct. Mol. Biol. 24, 809–815 (2017).
pubmed: 28892040
doi: 10.1038/nsmb.3465
Ehara, H. et al. Structure of the complete elongation complex of RNA polymerase II with basal factors. Science 357, 921–924 (2017).
pubmed: 28775211
doi: 10.1126/science.aan8552
Klein, B. J. et al. RNA polymerase and transcription elongation factor Spt4/5 complex structure. Proc. Natl Acad. Sci. USA 108, 546–550 (2011).
pubmed: 21187417
doi: 10.1073/pnas.1013828108
Martinez-Rucobo, F. W., Sainsbury, S., Cheung, A. C. & Cramer, P. Architecture of the RNA polymerase-Spt4/5 complex and basis of universal transcription processivity. EMBO J. 30, 1302–1310 (2011).
pubmed: 21386817
pmcid: 3094117
doi: 10.1038/emboj.2011.64
Belogurov, G. A. et al. Structural basis for converting a general transcription factor into an operon-specific virulence regulator. Mol. Cell 26, 117–129 (2007).
pubmed: 17434131
pmcid: 3116145
doi: 10.1016/j.molcel.2007.02.021
Kang, J. Y. et al. Structural basis for transcript elongation control by NusG family universal regulators. Cell 173, 1650–1662.e1614 (2018).
pubmed: 29887376
pmcid: 6003885
doi: 10.1016/j.cell.2018.05.017
Evrin, C. et al. Spt5 histone binding activity preserves chromatin during transcription by RNA polymerase II. EMBO J. 41, e109783 (2022).
pubmed: 35102600
pmcid: 8886531
doi: 10.15252/embj.2021109783
Fitz, J. et al. Spt5-mediated enhancer transcription directly couples enhancer activation with physical promoter interaction. Nat. Genet. 52, 505–515 (2020).
pubmed: 32251373
doi: 10.1038/s41588-020-0605-6
Maudlin, I. E. & Beggs, J. D. Spt5 modulates cotranscriptional spliceosome assembly in Saccharomyces cerevisiae. RNA 25, 1298–1310 (2019).
pubmed: 31289129
pmcid: 6800482
doi: 10.1261/rna.070425.119
Meyer, P. A. et al. Structures and functions of the multiple KOW domains of transcription elongation factor Spt5. Mol. Cell Biol. 35, 3354–3369 (2015).
pubmed: 26217010
pmcid: 4561723
doi: 10.1128/MCB.00520-15
Resto, M. et al. O-GlcNAcase is an RNA polymerase II elongation factor coupled to pausing factors SPT5 and TIF1beta. J. Biol. Chem. 291, 22703–22713 (2016).
pubmed: 27601472
pmcid: 5077205
doi: 10.1074/jbc.M116.751420
Mayer, A. et al. The spt5 C-terminal region recruits yeast 3’ RNA cleavage factor I. Mol. Cell Biol. 32, 1321–1331 (2012).
pubmed: 22290438
pmcid: 3302448
doi: 10.1128/MCB.06310-11
Webster, M. W. et al. Structural basis of transcription-translation coupling and collision in bacteria. Science 369, 1355–1359 (2020).
pubmed: 32820062
doi: 10.1126/science.abb5036
Wang, C. et al. Structural basis of transcription-translation coupling. Science 369, 1359–1365 (2020).
pubmed: 32820061
pmcid: 7566311
doi: 10.1126/science.abb5317
Wang, B., Gumerov, V. M., Andrianova, E. P., Zhulin, I. B. & Artsimovitch, I. Origins and molecular evolution of the NusG paralog RfaH. mBio 11, e02717–e02720 (2020).
pubmed: 33109766
pmcid: 7593976
doi: 10.1128/mBio.02717-20
Wang, B. & Artsimovitch, I. NusG, an ancient yet rapidly evolving transcription factor. Front. Microbiol. 11, 619618 (2020).
pubmed: 33488562
doi: 10.3389/fmicb.2020.619618
Bachman, M. A. et al. Genome-wide identification of Klebsiella pneumoniae fitness genes during lung infection. mBio 6, e00775 (2015).
pubmed: 26060277
pmcid: 4462621
doi: 10.1128/mBio.00775-15
Lawson, M. R. et al. Mechanism for the regulated control of bacterial transcription termination by a universal adaptor protein. Mol. Cell 71, 911–922.e914 (2018).
pubmed: 30122535
pmcid: 6151137
doi: 10.1016/j.molcel.2018.07.014
Bossi, L. et al. NusG prevents transcriptional invasion of H-NS-silenced genes. PLoS Genet. 15, e1008425 (2019).
pubmed: 31589608
pmcid: 6797219
doi: 10.1371/journal.pgen.1008425
Peters, J. M. et al. Rho and NusG suppress pervasive antisense transcription in Escherichia coli. Genes Dev. 26, 2621–2633 (2012).
pubmed: 23207917
pmcid: 3521622
doi: 10.1101/gad.196741.112
Sevostyanova, A., Belogurov, G. A., Mooney, R. A., Landick, R. & Artsimovitch, I. The beta subunit gate loop is required for RNA polymerase modification by RfaH and NusG. Mol. Cell 43, 253–262 (2011).
pubmed: 21777814
pmcid: 3142557
doi: 10.1016/j.molcel.2011.05.026
Belogurov, G. A., Mooney, R. A., Svetlov, V., Landick, R. & Artsimovitch, I. Functional specialization of transcription elongation factors. EMBO J. 28, 112–122 (2009).
pubmed: 19096362
doi: 10.1038/emboj.2008.268
Mori, M. et al. From coarse to fine: the absolute Escherichia coli proteome under diverse growth conditions. Mol. Syst. Biol. 17, e9536 (2021).
pubmed: 34032011
pmcid: 8144880
doi: 10.15252/msb.20209536
Bailey, M. J., Hughes, C. & Koronakis, V. RfaH and the ops element, components of a novel system controlling bacterial transcription elongation. Mol. Microbiol. 26, 845–851 (1997).
pubmed: 9426123
doi: 10.1046/j.1365-2958.1997.6432014.x
Artsimovitch, I. & Landick, R. The transcriptional regulator RfaH stimulates RNA chain synthesis after recruitment to elongation complexes by the exposed nontemplate DNA strand. Cell 109, 193–203 (2002).
pubmed: 12007406
doi: 10.1016/S0092-8674(02)00724-9
Zuber, P. K., Schweimer, K., Rosch, P., Artsimovitch, I. & Knauer, S. H. Reversible fold-switching controls the functional cycle of the antitermination factor RfaH. Nat. Commun. 10, 702 (2019).
pubmed: 30742024
pmcid: 6370827
doi: 10.1038/s41467-019-08567-6
Burmann, B. M. et al. An alpha helix to beta barrel domain switch transforms the transcription factor RfaH into a translation factor. Cell 150, 291–303 (2012).
pubmed: 22817892
pmcid: 3430373
doi: 10.1016/j.cell.2012.05.042
Zuber, P. K. et al. The universally-conserved transcription factor RfaH is recruited to a hairpin structure of the non-template DNA strand. eLife 7, e36349 (2018).
pubmed: 29741479
pmcid: 5995543
doi: 10.7554/eLife.36349
Artsimovitch, I. & Landick, R. Pausing by bacterial RNA polymerase is mediated by mechanistically distinct classes of signals. Proc. Natl Acad. Sci. USA 97, 7090–7095 (2000).
pubmed: 10860976
pmcid: 16504
doi: 10.1073/pnas.97.13.7090
Guo, X. et al. Structural basis for NusA stabilized transcriptional pausing. Mol. Cell 69, 816–827.e814 (2018).
pubmed: 29499136
pmcid: 5842316
doi: 10.1016/j.molcel.2018.02.008
Kang, J. Y. et al. Structural basis of transcription arrest by coliphage HK022 Nun in an Escherichia coli RNA polymerase elongation complex. eLife 6, e25478 (2017).
pubmed: 28318486
pmcid: 5386594
doi: 10.7554/eLife.25478
Larson, M. H. et al. A pause sequence enriched at translation start sites drives transcription dynamics in vivo. Science 344, 1042–1047 (2014).
pubmed: 24789973
pmcid: 4108260
doi: 10.1126/science.1251871
Vvedenskaya, I. O. et al. Interactions between RNA polymerase and the “core recognition element” counteract pausing. Science 344, 1285–1289 (2014).
pubmed: 24926020
pmcid: 4277259
doi: 10.1126/science.1253458
Abdelkareem, M. et al. Structural basis of transcription: RNA polymerase backtracking and its reactivation. Mol. Cell 75, 298–309.e294 (2019).
pubmed: 31103420
pmcid: 7611809
doi: 10.1016/j.molcel.2019.04.029
Saba, J. et al. The elemental mechanism of transcriptional pausing. eLife 8, e40981 (2019).
pubmed: 30618376
pmcid: 6336406
doi: 10.7554/eLife.40981
Artsimovitch, I. & Ramirez-Sarmiento, C. A. Metamorphic proteins under a computational microscope: lessons from a fold-switching RfaH protein. Comput. Struct. Biotechnol. J. 20, 5824–5837 (2022).
pubmed: 36382197
pmcid: 9630627
doi: 10.1016/j.csbj.2022.10.024
Lin, X. et al. Order and disorder control the functional rearrangement of influenza hemagglutinin. Proc. Natl Acad. Sci. USA 111, 12049–12054 (2014).
pubmed: 25082896
pmcid: 4143043
doi: 10.1073/pnas.1412849111
Galaz-Davison, P. et al. Differential local stability governs the metamorphic fold switch of bacterial virulence factor RfaH. Biophys. J. 118, 96–104 (2020).
pubmed: 31810657
doi: 10.1016/j.bpj.2019.11.014
Ramirez-Sarmiento, C. A., Noel, J. K., Valenzuela, S. L. & Artsimovitch, I. Interdomain contacts control native state switching of RfaH on a dual-funneled landscape. PLoS Comput. Biol. 11, e1004379 (2015).
pubmed: 26230837
pmcid: 4521827
doi: 10.1371/journal.pcbi.1004379
Tomar, S. K., Knauer, S. H., Nandymazumdar, M., Rosch, P. & Artsimovitch, I. Interdomain contacts control folding of transcription factor RfaH. Nucleic Acids Res. 41, 10077–10085 (2013).
pubmed: 23990324
pmcid: 3905879
doi: 10.1093/nar/gkt779
Shi, D., Svetlov, D., Abagyan, R. & Artsimovitch, I. Flipping states: a few key residues decide the winning conformation of the only universally conserved transcription factor. Nucleic Acids Res. 45, 8835–8843 (2017).
pubmed: 28605514
pmcid: 5587751
doi: 10.1093/nar/gkx523
Zuber, P. K. et al. Structural and thermodynamic analyses of the beta-to-alpha transformation in RfaH reveal principles of fold-switching proteins. eLife 11, e76630 (2022).
pubmed: 36255050
pmcid: 9683785
doi: 10.7554/eLife.76630
Galaz-Davison, P., Roman, E. A. & Ramirez-Sarmiento, C. A. The N-terminal domain of RfaH plays an active role in protein fold-switching. PLoS Comput. Biol. 17, e1008882 (2021).
pubmed: 34478435
pmcid: 8454952
doi: 10.1371/journal.pcbi.1008882
Gc, J. B., Gerstman, B. S. & Chapagain, P. P. The Role of the Interdomain Interactions on RfaH Dynamics and Conformational Transformation. J. Phys. Chem. B 119, 12750–12759 (2015).
pubmed: 26374226
doi: 10.1021/acs.jpcb.5b05681
Le, T. T. et al. Mfd dynamically regulates transcription via a release and catch-up mechanism. Cell 172, 344–357.e315 (2018).
pubmed: 29224782
doi: 10.1016/j.cell.2017.11.017
Wee, L. M. et al. A trailing ribosome speeds up RNA polymerase at the expense of transcript fidelity via force and allostery. Cell 186, 1244–1262.e1234 (2023).
pubmed: 36931247
pmcid: 10135430
doi: 10.1016/j.cell.2023.02.008
Wilson, K. S. & von Hippel, P. H. Transcription termination at intrinsic terminators: the role of the RNA hairpin. Proc. Natl Acad. Sci. USA 92, 8793–8797 (1995).
pubmed: 7568019
pmcid: 41053
doi: 10.1073/pnas.92.19.8793
Said, N. et al. Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase rho. Science 371, eabd1673 (2021).
pubmed: 33243850
doi: 10.1126/science.abd1673
Hao, Z. et al. Pre-termination transcription complex: structure and function. Mol. Cell 81, 281–292.e288 (2021).
pubmed: 33296676
doi: 10.1016/j.molcel.2020.11.013
Hu, K. & Artsimovitch, I. A screen for rfaH suppressors reveals a key role for a connector region of termination factor Rho. mBio 8, e00753–17 (2017).
pubmed: 28559482
pmcid: 5449661
doi: 10.1128/mBio.00753-17
Vishwakarma, R. K., Qayyum, M. Z., Babitzke, P. & Murakami, K. S. Allosteric mechanism of transcription inhibition by NusG-dependent pausing of RNA polymerase. Proc. Natl Acad. Sci. USA 120, e2218516120 (2023).
pubmed: 36745813
pmcid: 9963633
doi: 10.1073/pnas.2218516120
Delbeau, M. et al. Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis. Mol. Cell 83, 1474–1488.e1478 (2023).
pubmed: 37116494
doi: 10.1016/j.molcel.2023.04.007
Yakhnin, A. V., Murakami, K. S. & Babitzke, P. NusG is a sequence-specific RNA polymerase pause factor that binds to the non-template DNA within the paused transcription bubble. J. Biol. Chem. 291, 5299–5308 (2016).
pubmed: 26742846
pmcid: 4777861
doi: 10.1074/jbc.M115.704189
Turtola, M. & Belogurov, G. A. NusG inhibits RNA polymerase backtracking by stabilizing the minimal transcription bubble. eLife 5, e18096 (2016).
pubmed: 27697152
pmcid: 5100998
doi: 10.7554/eLife.18096
Pukhrambam, C. et al. Structural and mechanistic basis of sigma-dependent transcriptional pausing. Proc. Natl Acad. Sci. USA 119, e2201301119 (2022).
pubmed: 35653571
pmcid: 9191641
doi: 10.1073/pnas.2201301119
Belogurov, G. A., Sevostyanova, A., Svetlov, V. & Artsimovitch, I. Functional regions of the N-terminal domain of the antiterminator RfaH. Mol. Microbiol. 76, 286–301 (2010).
pubmed: 20132437
pmcid: 2871177
doi: 10.1111/j.1365-2958.2010.07056.x
Porter, L. L. et al. Many dissimilar NusG protein domains switch between alpha-helix and beta-sheet folds. Nat. Commun. 13, 3802 (2022).
pubmed: 35778397
pmcid: 9247905
doi: 10.1038/s41467-022-31532-9
de Marco, A. et al. Quality control of protein reagents for the improvement of research data reproducibility. Nat. Commun. 12, 2795 (2021).
pubmed: 33990604
pmcid: 8121922
doi: 10.1038/s41467-021-23167-z
Svetlov, V. & Artsimovitch, I. Purification of bacterial RNA polymerase: tools and protocols. Methods Mol. Biol. 1276, 13–29 (2015).
pubmed: 25665556
pmcid: 4324551
doi: 10.1007/978-1-4939-2392-2_2
Drogemuller, J. et al. Exploring RNA polymerase regulation by NMR spectroscopy. Sci. Rep. 5, 10825 (2015).
pubmed: 26043358
pmcid: 4650657
doi: 10.1038/srep10825
Strauss, M. et al. Transcription is regulated by NusA:NusG interaction. Nucleic Acids Res. 44, 5971–5982 (2016).
pubmed: 27174929
pmcid: 4937328
doi: 10.1093/nar/gkw423
Turtola, M., Makinen, J. J. & Belogurov, G. A. Active site closure stabilizes the backtracked state of RNA polymerase. Nucleic Acids Res. 46, 10870–10887 (2018).
pubmed: 30256972
pmcid: 6237748
Deaconescu, A. M. & Darst, S. A. Crystallization and preliminary structure determination of Escherichia coli Mfd, the transcription-repair coupling factor. Acta Crystallogr. F 61, 1062–1064 (2005).
doi: 10.1107/S1744309105035876
Meyer, O. & Schlegel, H. G. Biology of aerobic carbon monoxide-oxidizing bacteria. Annu. Rev. Microbiol 37, 277–310 (1983).
pubmed: 6416144
doi: 10.1146/annurev.mi.37.100183.001425
Anthis, N. J. & Clore, G. M. Sequence-specific determination of protein and peptide concentrations by absorbance at 205 nm. Protein Sci. 22, 851–858 (2013).
pubmed: 23526461
pmcid: 3690723
doi: 10.1002/pro.2253
Mori, S., Abeygunawardana, C., Johnson, M. O. & van Zijl, P. C. Improved sensitivity of HSQC spectra of exchanging protons at short interscan delays using a new fast HSQC (FHSQC) detection scheme that avoids water saturation. J. Magn. Reson B 108, 94–98 (1995).
pubmed: 7627436
doi: 10.1006/jmrb.1995.1109
Delaglio, F. et al. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277–293 (1995).
pubmed: 8520220
doi: 10.1007/BF00197809
Landick, R., Wang, D. & Chan, C. L. Quantitative analysis of transcriptional pausing by Escherichia coli RNA polymerase: his leader pause site as paradigm. Methods Enzymol. 274, 334–353 (1996).
pubmed: 8902817
doi: 10.1016/S0076-6879(96)74029-6
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
pubmed: 28165473
doi: 10.1038/nmeth.4169
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr D 60, 2126–2132 (2004).
pubmed: 15572765
doi: 10.1107/S0907444904019158
Echols, N. et al. Automating crystallographic structure solution and refinement of protein-ligand complexes. Acta Crystallogr. D 70, 144–154 (2014).
pubmed: 24419387
doi: 10.1107/S139900471302748X
Williams, C. J. et al. MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci. 27, 293–315 (2018).
pubmed: 29067766
doi: 10.1002/pro.3330
Pettersen, E. F. et al. UCSF ChimeraX: Structure visualization for researchers, educators, and developers. Protein Sci. 30, 70–82 (2021).
pubmed: 32881101
doi: 10.1002/pro.3943
Webb, B. & Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinform. 54, 5.6.1–5.6.37 (2016).
doi: 10.1002/cpbi.3
Pronk, S. et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845–854 (2013).
pubmed: 23407358
pmcid: 3605599
doi: 10.1093/bioinformatics/btt055
Lindorff-Larsen, K. et al. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 78, 1950–1958 (2010).
pubmed: 20408171
pmcid: 2970904
doi: 10.1002/prot.22711
Berendsen, H. J. C., Grigera, J. R. & Straatsma, T. P. The missing term in effective pair potentials. J. Phys. Chem. 91, 6269–6271 (1987).
doi: 10.1021/j100308a038
Noel, J. K., Whitford, P. C. & Onuchic, J. N. The shadow map: a general contact definition for capturing the dynamics of biomolecular folding and function. J. Phys. Chem. B 116, 8692–8702 (2012).
pubmed: 22536820
pmcid: 3406251
doi: 10.1021/jp300852d
Whitford, P. C. et al. An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields. Proteins 75, 430–441 (2009).
pubmed: 18837035
pmcid: 3439813
doi: 10.1002/prot.22253
Noel, J. K. et al. SMOG 2: a versatile software package for generating structure-based models. PLoS Comput. Biol. 12, e1004794 (2016).
pubmed: 26963394
pmcid: 4786265
doi: 10.1371/journal.pcbi.1004794
Lammert, H., Schug, A. & Onuchic, J. N. Robustness and generalization of structure-based models for protein folding and function. Proteins 77, 881–891 (2009).
pubmed: 19626713
doi: 10.1002/prot.22511
Dodero-Rojas, E., Onuchic, J. N. & Whitford, P. C. Sterically confined rearrangements of SARS-CoV-2 Spike protein control cell invasion. Elife 10, e70362 (2021).
Li, S., Olson, W. K. & Lu, X. J. Web 3DNA 2.0 for the analysis, visualization, and modeling of 3D nucleic acid structures. Nucleic Acids Res. 47, W26–W34 (2019).
pubmed: 31114927
pmcid: 6602438
doi: 10.1093/nar/gkz394