The crystal structure of a cardiovirus RNA-dependent RNA polymerase reveals an unusual conformation of the polymerase active site

Journal of Virology

Volumn 88, Issue 10, 2014, Pages 5595-5607

  Vives Adrian, Laia ^a,b   Lujan, Celia ^a   Oliva, Baldo ^c   van der Linden, Lonneke ^d,e,h   Selisko, Barbara ^f   Coutard, Bruno ^f   Canard, Bruno ^f   van Kuppeveld, Frank J M ^d,g   Ferrer Orta, Cristina ^a   Verdaguer, Núria ^a  

^a INSTITUT DE BIOLOGIA MOLECULAR DE BARCELONA   (Spain)

^b UNIVERSITY OF BARCELONA   (Spain)

^c UNIVERSITAT POMPEU FABRA   (Spain)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^f AIX MARSEILLE UNIVERSITY   (France)

^g UTRECHT UNIVERSITY   (Netherlands)

^h UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

RNA DIRECTED RNA POLYMERASE;

ALPHA HELIX; ARTICLE; BETA SHEET; BINDING AFFINITY; BINDING SITE; CARDIOVIRUS; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; NONHUMAN; PH; PICORNAVIRUS; PRIORITY JOURNAL; PROTEIN SECONDARY STRUCTURE; RNA REPLICATION; STRUCTURE ANALYSIS; VIROGENESIS; VIRUS REPLICATION;

CARDIOVIRUS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; PROTEIN CONFORMATION; RNA REPLICASE;

EID: 84899093998     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.03502-13     Document Type: Article

References (62)

1. Norder H, De Palma AM, Selisko B, Costenaro L, Papageorgiou N, Arnan C, Coutard B, Lantez V, De Lamballerie X, Baronti C, Sola M, Tan J, Neyts J, Canard B, Coll M, Gorbalenya AE, Hilgenfeld R. 2011. Picornavirus non-structural proteins as targets for new anti-virals with broad activity. Antiviral Res. 89:204-218. http://dx.doi.org/10.1016/j .antiviral.2010.12.007.
2. Knowles NJ, Hovi T, King AMQ, Stanway G. 2010. Overview of taxonomy, p 19-32. In Ehrenfeld E, Domingo E, Roos RP (ed), The picornaviruses. American Society for Microbiology, Washington, DC.
3. Duke GM, Hoffman MA, Palmenberg AC. 1992. Sequence and structural elements that contribute to efficient encephalomyocarditis virus RNA translation. J. Virol. 66:1602-1609.
4. Brahic M, Bureau JF, Michiels T. 2005. The genetics of the persistent infection and demyelinating disease caused by Theiler's virus. Annu. Rev. Microbiol. 59: 279-298. http://dx.doi.org/10.1146/annurev.micro.59.030804.121242.
5. Ohsawa K, Watanabe Y, Miyata H, Sato H. 2003. Genetic analysis of a Theiler-like virus isolated from rats. Comp. Med. 53:191-196. http://www .ncbi.nlm.nih.gov/pubmed/12784854.
6. Pritchard AE, Strom T, Lipton HL. 1992. Nucleotide sequence identifies Vilyuisk virus as a divergent Theiler's virus. Virology 191:469-472. http: //dx.doi.org/10.1016/0042-6822(92)90212-8.
7. Zimmerman JJ. 1994. Encephalomyocarditis, p 423-436. In Beran GW, Steele JH (ed),CRChandbook series in zoonoses.CRCPress, Boca Raton, FL.
8. Himeda T, Ohara Y. 2012. Saffold virus, a novel human Cardiovirus with unknown pathogenicity. J. Virol. 86:1292-1296. http://dx.doi.org/10 .1128/JVI.06087-11.
9. Jones MS, Lukashov VV, Ganac RD, Schnurr DP. 2007. Discovery of a novel human picornavirus in a stool sample from a pediatric patient presenting with fever of unknown origin. J. Clin. Microbiol. 45:2144-2150. http://dx.doi.org/10.1128/JCM.00174-07.
10. Liang Z, Kumar AS, Jones MS, Knowles NJ, Lipton HL. 2008. Phylogenetic analysis of the species Theilovirus: emerging murine andhumanpathogens. J. Virol. 82:11545-11554. http://dx.doi.org/10.1128/JVI.01160-08.
11. Blinkova O, Rosario K, Li L, Kapoor A, Slikas B, Bernardin F, Breitbart M, Delwart E. 2009. Frequent detection of highly diverse variants of cardiovirus, cosavirus, bocavirus, and circovirus in sewage samples collected in the United States. J. Clin. Microbiol. 47:3507-3513. http://dx.doi .org/10.1128/JCM.01062-09.
12. Zoll J, Erkens Hulshof S, Lanke K, Verduyn Lunel F, Melchers WJ, Schoondermark-van de Ven E, Roivainen M, Galama JM, van Kuppeveld FJ. 2009. Saffold virus, a human Theiler's-like cardiovirus, is ubiquitous and causes infection early in life. PLoS Pathog. 5:e1000416. http: //dx.doi.org/10.1371/journal.ppat.1000416.
13. Wu Y, Lou Z, Miao Y, Yu Y, Dong H, Peng W, Bartlam M, Li X, Rao Z. 2010. Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-footand-mouth disease pandemic in China. Protein Cell. 1:491-500. http://dx .doi.org/10.1007/s13238-010-0061-7.
14. Thompson AA, Peersen OB. 2004. Structural basis for proteolysisdependent activation of the poliovirus RNA-dependent RNA polymerase. EMBO J. 23:3462-3471. http://dx.doi.org/10.1038/sj.emboj.7600357.
15. Love RA, Maegley KA, Yu X, Ferre RA, Lingardo LK, Diehl W, Parge HE, Dragovich PS, Fuhrman SA. 2004. The crystal structure of the RNA-dependent RNA polymerase from human rhinovirus: a dual function target for common cold antiviral therapy. Structure 12:1533-1544. http://dx.doi.org/10.1016/j.str.2004.05.024.
16. Gruez A, Selisko B, Roberts M, Bricogne G, Bussetta C, Jabafi I, Coutard B, De Palma AM, Neyts J, Canard B. 2008. The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in complex with its protein primer VPg confirms the existence of a second VPg binding site on Picornaviridae polymerases. J. Virol. 82:9577-9590. http://dx.doi.org /10.1128/JVI.00631-08.
17. Gong P, Peersen OB. 2010. Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Proc. Natl. Acad. Sci. U. S. A. 107:22505-22510. http://dx.doi.org/10.1073/pnas.1007626107.
18. Gong P, Kortus MG, Nix JC, Davis RE, Peersen OB. 2013. Structures of coxsackievirus, rhinovirus, and poliovirus polymerase elongation complexes solved by engineering RNA mediated crystal contacts. PLoS One 8:e60272. http://dx.doi.org/10.1371/journal.pone.0060272.
19. Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N. 2007. Sequential structures provide insights into the fidelity of RNA replication. Proc. Natl. Acad. Sci. U. S. A. 104:9463-9468. http://dx .doi.org/10.1073/pnas.0700518104.
20. Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N. 2004. Structure of foot-and-mouth disease virus RNAdependent RNA polymerase and its complex with a template-primer RNA. J. Biol. Chem. 279:47212-47221. http://dx.doi.org/10.1074/jbc .M405465200.
21. Ferrer-Orta C, Arias A, Agudo R, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N. 2006. The structure of a protein primer-polymerase complex in the initiation of genome replication. EMBO J. 25:880-888. http://dx.doi.org/10.1038/sj.emboj.7600971.
22. Campagnola G, Weygandt M, Scoggin K, Peersen O. 2008. Crystal structure of coxsackievirus B3 3Dpol highlights the functional importance of residue 5 in picornavirus polymerases. J. Virol. 82:9458-9464. http://dx .doi.org/10.1128/JVI.00647-08.
23. Appleby TC, Luecke H, Shim JH, Wu JZ, Cheney IW, Zhong W, Vogeley L, Hong Z, Yao N. 2005. Crystal structure of complete rhinovirus RNA polymerase suggests front loading of protein primer. J. Virol. 79:277-288. http://dx.doi.org/10.1128/JVI.79.1.277-288.2005.
24. Ferrer-Orta C, Verdaguer N. 2009. RNA virus polymerases, p 383-401. In Cameron CE, g̈otte M, Raney KD (ed), Viral genome replication. Springer, New York, NY.
25. Garriga D, Ferrer-Orta C, Querol-Audi J, Oliva B, Verdaguer N. 2013. Role of motif B loop in allosteric regulation of RNA-dependent RNA polymerization activity. J. Mol. Biol. 425:2279-2287. http://dx.doi.org/10 .1016/j.jmb.2013.03.034.
26. Pfeiffer JK, Kirkegaard K. 2003. A single mutation in poliovirus RNAdependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity. Proc. Natl. Acad. Sci. U. S. A. 100:7289-7294. http://dx.doi.org/10.1073/pnas.1232294100.
27. Arnold JJ, Vignuzzi M, Stone JK, Andino R, Cameron CE. 2005. Remote site control of an active site fidelity checkpoint in a viral RNA-dependent RNA polymerase. J. Biol. Chem. 280:25706-25716. http://dx.doi.org/10 .1074/jbc.M503444200.
28. Agudo R, Ferrer-Orta C, Arias A, de la Higuera I, Perales C, Perez-Luque R, Verdaguer N, Domingo E. 2010. A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape. PLoS Pathog. 6:e1001072. http://dx .doi.org/10.1371/journal.ppat.1001072.
29. Marcotte LL, Wass AB, Gohara DW, Pathak HB, Arnold JJ, Filman DJ, Cameron CE, Hogle JM. 2007. Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase. J. Virol. 81:3583-3596. http://dx.doi.org/10.1128/JVI.02306-06.
30. Ferrer-Orta C, Sierra M, Agudo R, de la Higuera I, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N. 2010. Structure of foot-and-mouth disease virus mutant polymerases with reduced sensitivity to ribavirin. J. Virol. 84:6188-6199. http://dx.doi.org/10.1128/JVI .02420-09.
31. Moustafa IM, Shen H, Morton B, Colina CM, Cameron CE. 2011. Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity. J. Mol. Biol. 410:159-181. http://dx.doi.org/10.1016/j.jmb.2011.04.078.
32. Shen H, Sun H, Li G. 2012. What is the role of motif D in the nucleotide incorporation catalyzed by the RNA-dependent RNA polymerase from poliovirus? PLoS Comput. Biol. 8:e1002851. http://dx.doi.org/10.1371 /journal.pcbi.1002851.
33. Duke GM, Palmenberg AC. 1989. Cloning and synthesis of infectious cardiovirus RNAs containing short, discrete poly(C) tracts. J. Virol. 63: 1822-1826.
34. Lantez V, Dalle K, Charrel R, Baronti C, Canard B, Coutard B. 2011. Comparative production analysis of three phlebovirus nucleoproteins under denaturing or non-denaturing conditions for crystallographic studies. PLoS Negl. Trop. Dis. 5:e936. http://dx.doi.org/10.1371/journal.pntd .0000936.
35. Kabsch W. 2010. Xds. Acta Crystallogr. D Biol. Crystallogr. 66(Part 2): 125-132. http://dx.doi.org/10.1107/S0907444909047337.
36. Potterton E, Briggs P, Turkenburg M, Dodson E. 2003. A graphical user interface to the CCP4 program suite. Acta Crystallogr.DBiol. Crystallogr. 59(Part 7):1131-1137. http://dx.doi.org/10.1107/S0907444903008126.
37. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH. 2010. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66(Part 2):213-221. http://dx.doi.org/10.1107/S0907444909052925.
38. Emsley P, Lohkamp B, Scott WG, Cowtan K. 2010. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66(Part 4):486-501. http://dx.doi.org/10.1107/S0907444910007493.
39. Murshudov GN, Vagin AA, Dodson EJ. 1997. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53(Part 3):240 -255. http://dx.doi.org/10 .1107/S0907444996012255.
40. Golovanov AP, Hautbergue GM, Wilson SA, Lian LY. 2004. A simple method for improving protein solubility and long-term stability. J. Am. Chem. Soc. 126:8933-8939. http://dx.doi.org/10.1021/ja049297h.
41. Wiederstein M, Sippl MJ. 2007. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 35:W407-W410. http://dx.doi.org/10.1093/nar/gkm290.
42. Arias A, Agudo R, Ferrer-Orta C, Perez-Luque R, Airaksinen A, Brocchi E, Domingo E, Verdaguer N, Escarmis C. 2005. Mutant viral polymerase in the transition of virus to error catastrophe identifies a critical site for RNA binding. J. Mol. Biol. 353:1021-1032. http://dx.doi.org/10.1016/j .jmb.2005.09.022.
43. Ferrer-Orta C, Agudo R, Domingo E, Verdaguer N. 2009. Structural insights into replication initiation and elongation processes by the FMDV RNA-dependent RNA polymerase. Curr. Opin. Struct. Biol. 19:752-758. http://dx.doi.org/10.1016/j.sbi.2009.10.016.
44. Lescar J, Canard B. 2009. RNA-dependent RNA polymerases from flaviviruses and Picornaviridae. Curr. Opin. Struct. Biol. 19:759-767. http: //dx.doi.org/10.1016/j.sbi.2009.10.011.
45. Dmitrieva TM, Alexeevski AV, Shatskaya GS, Tolskaya EA, Gmyl AP, Khitrina EV, Agol VI. 2007. Significance of the C-terminal amino acid residue in mengovirus RNA-dependent RNA polymerase. Virology 365: 79-91. http://dx.doi.org/10.1016/j.virol.2007.02.038.
46. Kortus MG, Kempf BJ, Haworth KG, Barton DJ, Peersen OB. 2012. A template RNA entry channel in the fingers domain of the poliovirus polymerase. J. Mol. Biol. 417:263-278. http://dx.doi.org/10.1016/j.jmb.2012 .01.049.
47. Gohara DW, Crotty S, Arnold JJ, Yoder JD, Andino R, Cameron CE. 2000. Poliovirus RNA-dependent RNA polymerase (3Dpol): structural, biochemical, and biological analysis of conserved structural motifs A and B. J. Biol. Chem. 275:25523-25532. http://dx.doi.org/10 .1074/jbc.M002671200.
48. Gohara DW, Arnold JJ, Cameron CE. 2004. Poliovirus RNA-dependent RNA polymerase (3Dpol): kinetic, thermodynamic, and structural analysis of ribonucleotide selection. Biochemistry 43:5149-5158. http://dx.doi .org/10.1021/bi035429s.
49. Arnold JJ, Gohara DW, Cameron CE. 2004. Poliovirus RNA-dependent RNA polymerase (3Dpol): pre-steady-state kinetic analysis of ribonucleotide incorporation in the presence of Mn2 . Biochemistry 43:5138-5148. http://dx.doi.org/10.1021/bi035213q.
50. Castro C, Arnold JJ, Cameron CE. 2005. Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective. Virus Res. 107:141-149. http://dx.doi.org/10.1016 /j.virusres.2004.11.004.
51. Yang X, Smidansky ED, Maksimchuk KR, Lum D, Welch JL, Arnold JJ, Cameron CE, Boehr DD. 2012. Motif D of viral RNA-dependent RNA polymerases determines efficiency and fidelity of nucleotide addition. Structure 20:1519-1527. http://dx.doi.org/10.1016/j.str.2012.06.012.
52. Shen H, Moustafa IM, Cameron CE, Colina CM. 2012. Exploring the dynamics of four RNA-dependent RNA polymerases by a coarse-grained model. J. Phys. Chem. B 116:14515-14524. http://dx.doi.org/10.1021 /jp302709v.
53. Castro C, Smidansky ED, Arnold JJ, Maksimchuk KR, Moustafa IM, Uchida A, Götte M, Konigsberg W, Cameron CE. 2009. Nucleic acid polymerases use a general acid for nucleotidyl transfer. Nat. Struct. Mol. Biol. 16:212-218. http://dx.doi.org/10.1038/nsmb.1540.
54. Castro C, Smidansky E, Maksimchuk KR, Arnold JJ, Korneeva VS, Gotte M, Konigsberg W, Cameron CE. 2007. Two proton transfers in the transition state for nucleotidyl transfer catalyzed by RNA-and DNAdependent RNA and DNA polymerases. Proc. Natl. Acad. Sci. U. S. A. 104:4267-4272. http://dx.doi.org/10.1073/pnas.0608952104.
55. Verdaguer N, Ferrer-Orta C. 2012. Conformational changes in motif D of RdRps as fidelity determinant. Structure 20:1448-1450. http://dx.doi .org/10.1016/j.str.2012.08.014.
56. Ferrer-Orta C, Arias A, Escarmis C, Verdaguer N. 2006. A comparison of viral RNA-dependent RNA polymerases. Curr. Opin. Struct. Biol. 16: 27-34. http://dx.doi.org/10.1016/j.sbi.2005.12.002.
57. Hobson SD, Rosenblum ES, Richards OC, Richmond K, Kirkegaard K, Schultz SC. 2001. Oligomeric structures of poliovirus polymerase are important for function. EMBO J. 20:1153-1163. http://dx.doi.org/10 .1093/emboj/20.5.1153.
58. Rothstein MA, Richards OC, Amin C, Ehrenfeld E. 1988. Enzymatic activity of poliovirus RNA polymerase synthesized in Escherichia coli from viral cDNA. Virology 164:301-308. http://dx.doi.org/10.1016/0042 -6822(88)90542-9.
59. Sippl MJ. 1993. Recognition of errors in three-dimensional structures of proteins. Proteins 17:355-362. http://dx.doi.org/10.1002/prot.340170404.
60. Aloy P, Oliva B. 2009. Splitting statistical potentials into meaningful scoring functions: testing the prediction of near-native structures from decoy conformations. BMC Struct. Biol. 9:71. http://dx.doi.org/10.1186 /1472-6807-9-71.
61. Marti-Renom MA, Madhusudhan MS, Fiser A, Rost B, Sali A. 2002. Reliability of assessment of protein structure prediction methods. Structure 10:435-440. http://dx.doi.org/10.1016/S0969-2126(02)00731-1.
62. Sippl MJ. 1990. Calculation of conformational ensembles from potentials of mean force. An approach to the knowledge-based prediction of local structures in globular proteins. J. Mol. Biol. 213:859-883.