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What a twist: structural biology of the SARS-CoV-2 helicase nsp13

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 202-227 | Received 20 Jul 2023, Accepted 18 Jan 2024, Published online: 26 Feb 2024

References

  • Chan JF-W, Kok K-H, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9:221–236. doi:10.1080/22221751.2020.1719902
  • Abdelhaleem M. Helicases: An overview. In: Abdelhaleem MM, editor. Helicases: methods and protocols [Internet]. Totowa, NJ: Humana Press; 2010. p. 1–12. Available from: doi:10.1007/978-1-60327-355-8_1
  • Matson SW, Bean DW, George JW. DNA helicases: enzymes with essential roles in all aspects of DNA metabolism. BioEssays. 1994;16:13–22. doi:10.1002/bies.950160103
  • Martin R. S, Dale B W. Modularity and specialization in superfamily 1 and 2 helicases. J Bacteriol. 2002;184:1819–1826. doi:10.1128/JB.184.7.1819-1826.2002
  • Lehmann KC, Snijder EJ, Posthuma CC, et al. What we know but do not understand about nidovirus helicases. Virus Res. 2015;202:12–32. doi:10.1016/j.virusres.2014.12.001
  • Fairman-Williams ME, Guenther U-P, Jankowsky E. SF1 and SF2 helicases: family matters. Curr Opin Struct Biol. 2010;20:313–324. doi:10.1016/j.sbi.2010.03.011
  • Singleton MR, Dillingham MS, Wigley DB. Structure and mechanism of helicases and nucleic acid translocases. Annu Rev Biochem. 2007;76:23–50. doi:10.1146/annurev.biochem.76.052305.115300
  • Subramanya HS, Bird LE, Brannigan JA, et al. Crystal structure of a DExx box DNA helicase. Nature. 1996;384:379–383. doi:10.1038/384379a0
  • Korolev S, Hsieh J, Gauss GH, et al. Major domain swiveling revealed by the crystal structures of complexes of E. coli Rep helicase bound to single-stranded DNA and ADP. Cell. 1997;90:635–647. doi:10.1016/S0092-8674(00)80525-5
  • Kim JL, Morgenstern KA, Griffith JP, et al. Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. Structure. 1998;6:89–100. doi:10.1016/S0969-2126(98)00010-0
  • Velankar SS, Soultanas P, Dillingham MS, et al. Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell. 1999;97:75–84. doi:10.1016/S0092-8674(00)80716-3
  • Maluf NK, Fischer CJ, Lohman TM. A dimer of Escherichia coli UvrD is the active form of the helicase in vitro. J Mol Biol. 2003;325:913–935. doi:10.1016/S0022-2836(02)01277-9
  • Romano M, Ruggiero A, Squeglia F, et al. A structural view of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping. Cells. 2020;9:1267–1289.
  • Gorbalenya AE, Koonin EV. Viral proteins containing the purine NTP-binding sequence pattern. Nucleic Acids Res. 1989;17:8413–8438. doi:10.1093/nar/17.21.8413
  • Anja S, van Dinten Leonie C, Snijder EJ, et al. Biochemical characterization of the equine arteritis virus helicase suggests a close functional relationship between arterivirus and coronavirus helicases. J. Virol. 2000;74:9586–9593. doi:10.1128/JVI.74.20.9586-9593.2000
  • Seybert A, Hegyi A, Siddell SG, et al. The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex-unwinding activities with 5′-to-3′ polarity. RNA. 2000;6:1056–1068.
  • Tanner JA, Watt RM, Chai Y-B, et al. The severe acute respiratory syndrome (SARS) coronavirus NTPase/helicase belongs to a distinct class of 5′ to 3′ viral helicases. J Biol Chem. 2003;278:39578–39582. doi:10.1074/jbc.C300328200
  • Konstantin A I, John Z. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding,: nucleoside triphosphatase, and RNA 5′-triphosphatase activities. J Virol. 2004;78:7833–7838. doi:10.1128/JVI.78.14.7833-7838.2004
  • Lee N-R, Kwon H-M, Park K, et al. Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13. Nucleic Acids Res. 2010;38:7626–7636. doi:10.1093/nar/gkq647
  • Subissi L, Imbert I, Ferron F, et al. SARS-CoV ORF1b-encoded nonstructural proteins 12–16: replicative enzymes as antiviral targets. Antiviral Res. 2014;101:122–130. doi:10.1016/j.antiviral.2013.11.006
  • Anja S, Clara C. P, Leonie C. vD, et al. A complex zinc finger controls the enzymatic activities of nidovirus helicases. J Virol. 2005;79:696–704. doi:10.1128/JVI.79.2.696-704.2005
  • Hajikhezri Z, Darweesh M, Akusjärvi G, et al. Role of CCCH-type zinc finger proteins in human adenovirus infections. Viruses. 2020;12:1322–1335.
  • Fu M, Blackshear PJ. RNA-binding proteins in immune regulation: a focus on CCCH zinc finger proteins. Nat Rev Immunol. 2017;17:130–143. doi:10.1038/nri.2016.129
  • van Dinten LC, van Tol H, Gorbalenya AE, et al. The predicted metal-binding region of the arterivirus helicase protein is involved in subgenomic mRNA synthesis, genome replication, and virion biogenesis. J Virol. 2000;74:5213–5223. doi:10.1128/JVI.74.11.5213-5223.2000
  • Walker JE, Saraste M, Runswick MJ, et al. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1982;1:945–951. doi:10.1002/j.1460-2075.1982.tb01276.x
  • Caruthers JM, McKay DB. Helicase structure and mechanism. Curr Opin Struct Biol. 2002;12:123–133. doi:10.1016/S0959-440X(02)00298-1
  • Gorbalenya AE, Koonin EV. Helicases: amino acid sequence comparisons and structure-function relationships. Curr Opin Struct Biol. 1993;3:419–429. doi:10.1016/S0959-440X(05)80116-2
  • Adedeji AO, Marchand B, te Velthuis AJW, et al. Mechanism of nucleic acid unwinding by SARS-CoV helicase. PLoS One. 2012;7:e36521. doi:10.1371/journal.pone.0036521
  • Jia Z, Yan L, Ren Z, et al. Delicate structural coordination of the severe acute respiratory syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res. 2019;47:6538–6550. doi:10.1093/nar/gkz409
  • Chen J, Malone B, Llewellyn E, et al. Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex. Cell. 2020;182:1560.e13–1573.e13. doi:10.1016/j.cell.2020.07.033
  • Konstantin A. I, Volker T, Jessika C. D, et al. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J Virol. 2004;78:5619–5632. doi:10.1128/JVI.78.11.5619-5632.2004
  • Yan L, Huang Y, Ge J, et al. A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors. Cell. 2022;185:4347.e17–4360.e17. doi:10.1016/j.cell.2022.09.037
  • Park GJ, Osinski A, Hernandez G, et al. The mechanism of RNA capping by SARS-CoV-2. Nature. 2022;609:793–800.
  • Hao W, Wojdyla JA, Zhao R, et al. Crystal structure of Middle East respiratory syndrome coronavirus helicase. PLoS Pathog. 2017;13:e1006474. doi:10.1371/journal.ppat.1006474
  • Berta D, Badaoui M, Martino SA, et al. Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design. Chem Sci. 2021;12:13492–13505. doi:10.1039/D1SC02775A
  • Klug A. Zinc finger peptides for the regulation of gene expression. J Mol Biol. 1999;293:215–218. doi:10.1006/jmbi.1999.3007
  • Matthews JM, Sunde M. Zinc fingers--folds for many occasions. IUBMB Life. 2002;54:351–355. doi:10.1080/15216540216035
  • Brown RS. Zinc finger proteins: getting a grip on RNA. Curr Opin Struct Biol. 2005;15:94–98. doi:10.1016/j.sbi.2005.01.006
  • Hall TMT. Multiple modes of RNA recognition by zinc finger proteins. Curr Opin Struct Biol. 2005;15:367–373. doi:10.1016/j.sbi.2005.04.004
  • Gamsjaeger R, Liew CK, Loughlin FE, et al. Sticky fingers: zinc-fingers as protein-recognition motifs. Trends Biochem Sci. 2007;32:63–70. doi:10.1016/j.tibs.2006.12.007
  • Grishin NV. Treble clef finger–a functionally diverse zinc-binding structural motif. Nucleic Acids Res. 2001;29:1703–1714. doi:10.1093/nar/29.8.1703
  • Newman JA, Douangamath A, Yadzani S, et al. Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase. Nat Commun. 2021;12:4848–4859. doi:10.1038/s41467-021-25166-6
  • Coles M, Hulko M, Djuranovic S, et al. Common evolutionary origin of swapped-hairpin and double-Psi β barrels. Structure. 2006;14:1489–1498. doi:10.1016/j.str.2006.08.005
  • Cheng Z, Muhlrad D, Lim MK, et al. Structural and functional insights into the human Upf1 helicase core. EMBO J. 2007;26:253–264. doi:10.1038/sj.emboj.7601464
  • Deng Z, Lehmann KC, Li X, et al. Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase. Nucleic Acids Res. 2014;42:3464–3477. doi:10.1093/nar/gkt1310
  • Berman HM, Westbrook J, Feng Z, et al. The protein data bank. Nucleic Acids Res. 2000;28:235–242. doi:10.1093/nar/28.1.235
  • Williams CJ, Headd JJ, Moriarty NW, et al. Molprobity: more and better reference data for improved all-atom structure validation. Protein Sci. 2018;27:293–315. doi:10.1002/pro.3330
  • White MA, Lin W, Cheng X. Discovery of COVID-19 inhibitors targeting the SARS-CoV-2 Nsp13 helicase. J Phys Chem Lett. 2020;11:9144–9151. doi:10.1021/acs.jpclett.0c02421
  • Croll TI, Diederichs K, Fischer F, et al. Making the invisible enemy visible. Nat Struct Mol Biol. 2021;28:404–408. doi:10.1038/s41594-021-00593-7
  • Weber R, McCullagh M. Role of ATP in the RNA translocation mechanism of SARS-CoV-2 NSP13 helicase. J Phys Chem B. 2021;125:8787–8796. doi:10.1021/acs.jpcb.1c04528
  • Sommers JA, Loftus LN. Jones MP, III. et al. Biochemical analysis of SARS-CoV-2 Nsp13 helicase implicated in COVID-19 and factors that regulate its catalytic functions. J Biol Chem. 2023;299:102980–10299. doi:10.1016/j.jbc.2023.102980
  • Yu J, Ha T, Schulten K. Structure-based model of the stepping motor of PcrA helicase. Biophys J. 2006;91:2097–2114. doi:10.1529/biophysj.106.088203
  • Dillingham MS, Soultanas P, Wiley P, et al. Defining the roles of individual residues in the single-stranded DNA binding site of PcrA helicase. Proc Natl Acad Sci. 2001;98:8381–8387. doi:10.1073/pnas.131009598
  • Saikrishnan K, Powell B, Cook NJ, et al. Mechanistic basis of 5′-3′ translocation in SF1B helicases. Cell. 2009;137:849–859. doi:10.1016/j.cell.2009.03.036
  • Yue K, Yao B, Shi Y, et al. The stalk domain of SARS-CoV-2 NSP13 is essential for its helicase activity. Biochem Biophys Res Commun. 2022;601:129–136. doi:10.1016/j.bbrc.2022.02.068
  • Wang D, Bushnell DA, Huang X, et al. Structural basis of transcription: backtracked RNA polymerase II at 3.4 Angstrom resolution. Science. 2009;324:1203–1206. doi:10.1126/science.1168729
  • Nudler E. Rna polymerase backtracking in gene regulation and genome instability. Cell. 2012;149:1438–1445. doi:10.1016/j.cell.2012.06.003
  • Malone B, Chen J, Wang Q, et al. Structural basis for backtracking by the SARS-CoV-2 replication–transcription complex. Proc Natl Acad Sci. 2021;118:e2102516118. doi:10.1073/pnas.2102516118
  • Chen J, Wang Q, Malone B, et al. Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication–transcription complex. Nat Struct Mol Biol. 2022;29:250–260. doi:10.1038/s41594-022-00734-6
  • Lane WJ, Darst SA. Molecular evolution of multisubunit RNA polymerases: structural analysis. J Mol Biol. 2010;395:686–704. doi:10.1016/j.jmb.2009.10.063
  • Bruenn JA. A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucleic Acids Res. 2003;31:1821–1829. doi:10.1093/nar/gkg277
  • Kang JY, Olinares PDB, Chen J, et al. Structural basis of transcription arrest by coliphage HK022 Nun in an escherichia coli RNA polymerase elongation complex. eLife. 2017;6:e25478.
  • Nakayama H. Recq family helicases: roles as tumor suppressor proteins. Oncogene. 2002;21:9008–9021. doi:10.1038/sj.onc.1205959
  • Adeyemi O. A, Kamalendra S, Calcaterra NE, et al. Severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase. Antimicrob Agents Chemother. 2012;56:4718–4728. doi:10.1128/AAC.00957-12
  • Caruthers JM, Johnson ER, McKay DB. Crystal structure of yeast initiation factor 4A, a DEAD-box RNA helicase. Proc Natl Acad Sci. 2000;97:13080–13085. doi:10.1073/pnas.97.24.13080
  • Wang Y, Wagner JDO, Guthrie C. The DEAH-box splicing factor Prp16 unwinds RNA duplexes in vitro. Curr Biol. 1998;8:441–451. doi:10.1016/S0960-9822(98)70178-2
  • Frick DN. Helicases as antiviral drug targets. Drug News Perspect. 2003;16:355–362. doi:10.1358/dnp.2003.16.6.829307
  • Yazdani S, De Maio N, Ding Y, et al. Genetic variability of the SARS-CoV-2 pocketome. J Proteome Res. 2021;20:4212–4215. doi:10.1021/acs.jproteome.1c00206
  • Tanner JA, Zheng B-J, Zhou J, et al. The adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus. Chem Biol. 2005;12:303–311. doi:10.1016/j.chembiol.2005.01.006
  • Yang N, Tanner JA, Wang Z, et al. Inhibition of SARS coronavirus helicase by bismuth complexes. Chem Commun. 2007;14(42):4413–4415. doi:10.1039/b709515e
  • Yang N, Tanner JA, Zheng B-J, et al. Bismuth complexes inhibit the SARS coronavirus. Angew Cheme Int Ed. 2007;46:6464–6468. doi:10.1002/anie.200701021
  • Lee C, Lee JM, Lee N-R, et al. Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase. Bioorg Med Chem Lett. 2009;19:1636–1638. doi:10.1016/j.bmcl.2009.02.010
  • Yu M-S, Lee J, Lee JM, et al. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsp13. Bioorg Med Chem Lett. 2012;22:4049–4054. doi:10.1016/j.bmcl.2012.04.081
  • Chuan-hai ZHANG, Yi-fei WANG, Xin-jian LIU, et al. Antiviral activity of cepharanthine against severe acute respiratory syndrome coronavirus in vitro. Chin Med J. 2005;118:493–496.
  • Fan H-H, Wang L-Q, Liu W-L, et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model. Chin Med J [Internet]. 2020;133:1051–1056. https://journals.lww.com/cmj/Fulltext/2020/05050/Repurposing_of_clinically_approved_drugs_for.8.aspx
  • Zeng J, Weissmann F, Bertolin AP, et al. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp13 helicase. Biochem J. 2021;478:2405–2423. doi:10.1042/BCJ20210201
  • Brun R, Blum J, Chappuis F, et al. Human African trypanosomiasis. Lancet. 2010;375:148–159. doi:10.1016/S0140-6736(09)60829-1
  • Natalie W, Dennis A. H. Mäser pascal 100 years of suramin. Antimicrob Agents Chemother. 2020;64:e01168–19.
  • Clarisse S-B, Melissa T, Ali T, et al. Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle. Antimicrob Agents Chemother. 2020;64:e00900–20.
  • Yan L, Zhang Y, Ge J, et al. Architecture of a SARS-CoV-2 mini replication and transcription complex. Nat Commun. 2020;11:5874–5880. doi:10.1038/s41467-020-19770-1
  • Tabor S, Richardson CC. Template recognition sequence for RNA primer synthesis by gene 4 protein of bacteriophage T7. Proc Natl Acad Sci. 1981;78:205–209. doi:10.1073/pnas.78.1.205

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