#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Determining the molecular drivers of species-specific interferon-stimulated gene product 15 interactions with nairovirus ovarian tumor domain proteases


Autoři: John V. Dzimianski aff001;  Florine E. M. Scholte aff002;  Isabelle L. Williams aff001;  Caroline Langley aff001;  Brendan T. Freitas aff001;  Jessica R. Spengler aff002;  Éric Bergeron aff002;  Scott D. Pegan aff001
Působiště autorů: Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, United States of America aff001;  Division of High Consequence Pathogens and Pathology, Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0226415

Souhrn

Tick-borne nairoviruses (order Bunyavirales) encode an ovarian tumor domain protease (OTU) that suppresses the innate immune response by reversing the post-translational modification of proteins by ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15). Ub is highly conserved across eukaryotes, whereas ISG15 is only present in vertebrates and shows substantial sequence diversity. Prior attempts to address the effect of ISG15 diversity on viral protein-ISG15 interactions have focused on only a single species’ ISG15 or a limited selection of nairovirus OTUs. To gain a more complete perspective of OTU-ISG15 interactions, we biochemically assessed the relative activities of 14 diverse nairovirus OTUs for 12 species’ ISG15 and found that ISG15 activity is predominantly restricted to particular nairovirus lineages reflecting, in general, known virus-host associations. To uncover the underlying molecular factors driving OTUs affinity for ISG15, X-ray crystal structures of Kupe virus and Ganjam virus OTUs bound to sheep ISG15 were solved and compared to complexes of Crimean-Congo hemorrhagic fever virus and Erve virus OTUs bound to human and mouse ISG15, respectively. Through mutational and structural analysis seven residues in ISG15 were identified that predominantly influence ISG15 species specificity among nairovirus OTUs. Additionally, OTU residues were identified that influence ISG15 preference, suggesting the potential for viral OTUs to adapt to different host ISG15s. These findings provide a foundation to further develop research methods to trace nairovirus-host relationships and delineate the full impact of ISG15 diversity on nairovirus infection.

Klíčová slova:

Electrostatics – Fruit bats – Host-pathogen interactions – Livestock – Sequence alignment – Sheep – Vertebrates – Shrews


Zdroje

1. Maes P, Adkins S, Alkhovsky SV, Avsic-Zupanc T, Ballinger MJ, Bente DA, et al. Taxonomy of the order Bunyavirales: second update 2018. Arch Virol. 2019;164(3):927–41. Epub 2019/01/22. doi: 10.1007/s00705-018-04127-3 30663021.

2. Maes P, Alkhovsky SV, Bao Y, Beer M, Birkhead M, Briese T, et al. Taxonomy of the family Arenaviridae and the order Bunyavirales: update 2018. Arch Virol. 2018;163(8):2295–310. doi: 10.1007/s00705-018-3843-5 29680923.

3. Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M. Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res. 2013;100(1):159–89. Epub 2013/08/03. doi: 10.1016/j.antiviral.2013.07.006 23906741.

4. Burt FJ, Spencer DC, Leman PA, Patterson B, Swanepoel R. Investigation of tick-borne viruses as pathogens of humans in South Africa and evidence of Dugbe virus infection in a patient with prolonged thrombocytopenia. Epidemiol Infect. 1996;116(3):353–61. Epub 1996/06/01. doi: 10.1017/s0950268800052687 8666081; PubMed Central PMCID: PMC2271429.

5. Dandawate CN, Work TH, Webb JK, Shah KV. Isolation of Ganjam virus from a human case of febrile illness: a report of a laboratory infection and serological survey of human sera from three different states of India. Indian J Med Res. 1969;57(6):975–82. Epub 1969/06/01. 5823182.

6. Kalunda M, Mukwaya LG, Mukuye A, Lule M, Sekyalo E, Wright J, et al. Kasokero virus: a new human pathogen from bats (Rousettus aegyptiacus) in Uganda. Am J Trop Med Hyg. 1986;35(2):387–92. Epub 1986/03/01. doi: 10.4269/ajtmh.1986.35.387 3082234.

7. L'Vov D K, Kostiukov MA, Daniiarov OA, Tukhtaev TM, Sherikov BK. [Outbreak of arbovirus infection in the Tadzhik SSR due to the Issyk-Kul virus (Issyk-Kul fever)]. Vopr Virusol. 1984;29(1):89–92. Epub 1984/01/01. 6143452.

8. Rao CV, Dandawate CN, Rodrigues JJ, Rao GL, Mandke VB, Ghalsasi GR, et al. Laboratory infections with Ganjam virus. Indian J Med Res. 1981;74:319–24. Epub 1981/09/01. 6797936.

9. Treib J, Dobler G, Haass A, von Blohn W, Strittmatter M, Pindur G, et al. Thunderclap headache caused by Erve virus? Neurology. 1998;50(2):509–11. Epub 1998/03/04. doi: 10.1212/wnl.50.2.509 9484383.

10. Spengler JR, Bergeron E, Rollin PE. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals. PLoS Negl Trop Dis. 2016;10(1):e0004210. Epub 2016/01/08. doi: 10.1371/journal.pntd.0004210 26741652; PubMed Central PMCID: PMC4704823.

11. Spengler JR, Estrada-Pena A, Garrison AR, Schmaljohn C, Spiropoulou CF, Bergeron E, et al. A chronological review of experimental infection studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus. Antiviral Res. 2016;135:31–47. Epub 2016/10/28. doi: 10.1016/j.antiviral.2016.09.013 27713073; PubMed Central PMCID: PMC5102700.

12. Davies FG. Nairobi sheep disease. Parassitologia. 1997;39(2):95–8. Epub 1997/06/01. 9530691.

13. Ishii A, Ueno K, Orba Y, Sasaki M, Moonga L, Hang'ombe BM, et al. A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice. Nat Commun. 2014;5:5651. Epub 2014/12/03. doi: 10.1038/ncomms6651 25451856; PubMed Central PMCID: PMC4268697.

14. Montgomery E. On a Tick-borne Gastroenteritis of Sheep and Goats occurring in British East Africa. Journal of Comparative Pathology and Therapeutics. 1917;30(1):28–57.

15. Converse JD, Hoogstraal H, Moussa MI, Feare CJ, Kaiser MN. Soldado virus (Hughes group) from Ornithodoros (Alectorobius) capensis (Ixodoidea: Argasidae) infesting Sooty Tern colonies in the Seychelles, Indian Ocean. Am J Trop Med Hyg. 1975;24(6 Pt 1):1010–8. Epub 1975/11/01. doi: 10.4269/ajtmh.1975.24.1010 1200252.

16. Crabtree MB, Sang R, Miller BR. Kupe virus, a new virus in the family bunyaviridae, genus nairovirus, kenya. Emerg Infect Dis. 2009;15(2):147–54. Epub 2009/02/06. doi: 10.3201/eid1502.080851 19193256; PubMed Central PMCID: PMC2657624.

17. Sang R, Onyango C, Gachoya J, Mabinda E, Konongoi S, Ofula V, et al. Tickborne arbovirus surveillance in market livestock, Nairobi, Kenya. Emerg Infect Dis. 2006;12(7):1074–80. Epub 2006/07/14. doi: 10.3201/eid1207.060253 16836823; PubMed Central PMCID: PMC3291068.

18. Durfee LA, Lyon N, Seo K, Huibregtse JM. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. Mol Cell. 2010;38:722–32. Epub 2010/06/15. doi: 10.1016/j.molcel.2010.05.002 20542004.

19. Bakshi S, Holzer B, Bridgen A, McMullan G, Quinn DG, Baron MD. Dugbe virus ovarian tumour domain interferes with ubiquitin/ISG15-regulated innate immune cell signalling. J Gen Virol. 2013;94(Pt 2):298–307. Epub 2012/11/09. doi: 10.1099/vir.0.048322-0 23136361; PubMed Central PMCID: PMC3709621.

20. Frias-Staheli N, Giannakopoulos NV, Kikkert M, Taylor SL, Bridgen A, Paragas J, et al. Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host and Microbe. 2007;2:404–16. doi: 10.1016/j.chom.2007.09.014 18078692

21. Holzer B, Bakshi S, Bridgen A, Baron MD. Inhibition of interferon induction and action by the nairovirus Nairobi sheep disease virus/Ganjam virus. PLoS One. 2011;6(12):e28594. Epub 2011/12/14. doi: 10.1371/journal.pone.0028594 22163042; PubMed Central PMCID: PMC3230622.

22. Scholte FEM, Zivcec M, Dzimianski JV, Deaton MK, Spengler JR, Welch SR, et al. Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease. Cell Rep. 2017;20(10):2396–407. Epub 2017/09/07. doi: 10.1016/j.celrep.2017.08.040 28877473; PubMed Central PMCID: PMC5616139.

23. Arimoto K-iI, Löchte S, Stoner SA, Burkart C, Zhang Y, Miyauchi S, et al. STAT2 is an essential adaptor in USP18-mediated suppression of type i interferon signaling. Nature Structural & Molecular Biology. 2017;24:279–89. doi: 10.1038/nsmb.3378 28165510.

24. Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D, et al. Mycobacterial Disease and Impaired IFN-ɣ Immunity in Humans with Inherited ISG15 Deficiency. Science. 2012;2:1684–9.

25. D'Cunha J, Ramanujam S, Wagner RJ, Witt PL, Knight E Jr, Borden EC. In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol. 1996;157:4100–8. Epub 1996/11/01. 8892645.

26. Du Y, Duan T, Feng Y, Liu Q, Lin M, Cui J, et al. LRRC25 inhibits type I IFN signaling by targeting ISG15‐associated RIG‐I for autophagic degradation. The EMBO Journal. 2017:e96781. doi: 10.15252/embj.201796781 29288164

27. Knight E Jr, Cordova B. IFN-induced 15-kDa protein is released from human lymphocytes and monocytes. J Immunol. 1991;146:2280–4. Epub 1991/04/01. 2005397.

28. Malakhov MP, Malakhova OA, Kim KI, Ritchie KJ, Zhang DE. UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem. 2002;277:9976–81. Epub 2002/01/15. doi: 10.1074/jbc.M109078200 11788588.

29. Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, et al. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev. 2003;17:455–60. Epub 2003/02/26. doi: 10.1101/gad.1056303 12600939.

30. Recht M, Borden EC, Knight E Jr. A human 15-kDa IFN-induced protein induces the secretion of IFN-gamma. J Immunol. 1991;147:2617–23. Epub 1991/10/25. 1717569.

31. Speer SD, Li Z, Buta S, Payelle-Brogard B, Qian L, Vigant F, et al. ISG15 deficiency and increased viral resistance in humans but not mice. Nat Commun. 2016;7:11496. Epub 2016/05/20. doi: 10.1038/ncomms11496 27193971.

32. Swaim CD, Scott AF, Canadeo LA, Huibregtse JM. Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor. Mol Cell. 2017;68(3):581–90 e5. Epub 2017/11/04. doi: 10.1016/j.molcel.2017.10.003 29100055; PubMed Central PMCID: PMC5690536.

33. Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, et al. Human intracellular ISG15 prevents interferon-alpha/beta over-amplification and auto-inflammation. Nature. 2015;517(7532):89–93. Epub 2014/10/14. doi: 10.1038/nature13801 25307056; PubMed Central PMCID: PMC4303590.

34. Daczkowski CM, Dzimianski JV, Clasman JR, Goodwin O, Mesecar AD, Pegan SD. Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. J Mol Biol. 2017;429(11):1661–83. Epub 2017/04/26. doi: 10.1016/j.jmb.2017.04.011 28438633; PubMed Central PMCID: PMC5634334.

35. Jiang Y, Wang X. Structural insights into the species preference of the influenza B virus NS1 protein in ISG15 binding. Protein & cell. 2018. doi: 10.1007/s13238-018-0598-4 30519829.

36. Langley C, Goodwin O, Dzimianski JV, Daczkowski CM, Pegan SD. Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement. Acta Crystallographica Section D Structural Biology. 2019;75. doi: 10.1107/S2059798318016492

37. Dzimianski JV, Scholte FEM, Bergeron É, Pegan SD. ISG15: it's Complicated. Journal of Molecular Biology. 2019. https://doi.org/10.1016/j.jmb.2019.03.013.

38. Deaton MK, Dzimianski JV, Daczkowski CM, Whitney GK, Mank NJ, Parham MM, et al. Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species. J Virol. 2016;90(18):8314–27. Epub 2016/07/15. doi: 10.1128/JVI.00975-16 27412597; PubMed Central PMCID: PMC5008091.

39. Daczkowski CM, Goodwin OY, Dzimianski JV, Farhat JJ, Pegan SD. Structurally Guided Removal of DeISGylase Biochemical Activity from Papain-Like Protease Originating from Middle East Respiratory Syndrome Coronavirus. J Virol. 2017;91. Epub 2017/09/22. doi: 10.1128/JVI.01067-17 28931677.

40. Deaton MK, Spear A, Faaberg KS, Pegan SD. The vOTU domain of highly-pathogenic porcine reproductive and respiratory syndrome virus displays a differential substrate preference. Virology. 2014;454–455:247–53. Epub 2014/04/15. doi: 10.1016/j.virol.2014.02.026 24725951.

41. Dzimianski JV, Beldon BS, Daczkowski CM, Goodwin OY, Scholte FEM, Bergeron E, et al. Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity. PLoS Pathog. 2019;15(1):e1007515. Epub 2019/01/11. doi: 10.1371/journal.ppat.1007515 30629698; PubMed Central PMCID: PMC6343935.

42. Walker PJ, Widen SG, Wood TG, Guzman H, Tesh RB, Vasilakis N. A Global Genomic Characterization of Nairoviruses Identifies Nine Discrete Genogroups with Distinctive Structural Characteristics and Host-Vector Associations. Am J Trop Med Hyg. 2016;94(5):1107–22. Epub 2016/02/24. doi: 10.4269/ajtmh.15-0917 26903607; PubMed Central PMCID: PMC4856612.

43. Akutsu M, Ye Y, Virdee S, Chin JW, Komander D. Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains. Proc Natl Acad Sci U S A. 2011;108(6):2228–33. Epub 2011/01/27. doi: 10.1073/pnas.1015287108 21266548; PubMed Central PMCID: PMC3038727.

44. Capodagli GC, Deaton MK, Baker EA, Lumpkin RJ, Pegan SD. Diversity of ubiquitin and ISG15 specificity among nairoviruses' viral ovarian tumor domain proteases. J Virol. 2013;87(7):3815–27. Epub 2013/01/25. doi: 10.1128/JVI.03252-12 23345508; PubMed Central PMCID: PMC3624237.

45. Capodagli GC, McKercher MA, Baker EA, Masters EM, Brunzelle JS, Pegan SD. Structural analysis of a viral ovarian tumor domain protease from the Crimean-Congo hemorrhagic fever virus in complex with covalently bonded ubiquitin. J Virol. 2011;85(7):3621–30. Epub 2011/01/14. doi: 10.1128/JVI.02496-10 21228232; PubMed Central PMCID: PMC3067871.

46. James TW, Frias-Staheli N, Bacik J-P, Levingston Macleod JM, Khajehpour M, García-Sastre A, et al. Structural basis for the removal of ubiquitin and interferon-stimulated gene 15 by a viral ovarian tumor domain-containing protease. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:2222–7. doi: 10.1073/pnas.1013388108 21245344

47. Choy A, Severo MS, Sun R, Girke T, Gillespie JJ, Pedra JH. Decoding the ubiquitin-mediated pathway of arthropod disease vectors. PLoS One. 2013;8(10):e78077. Epub 2013/11/10. doi: 10.1371/journal.pone.0078077 24205097; PubMed Central PMCID: PMC3804464.

48. Zhao C, Sridharan H, Chen R, Baker DP, Wang S, Krug RM. Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins. Nat Commun. 2016;7:12754. Epub 2016/09/03. doi: 10.1038/ncomms12754 27587337.

49. Guan R, Ma LC, Leonard PG, Amer BR, Sridharan H, Zhao C, et al. Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus. Proc Natl Acad Sci U S A. 2011;108:13468–73. Epub 2011/08/03. doi: 10.1073/pnas.1107032108 21808041.

50. Sridharan H, Zhao C, Krug RM. Species specificity of the NS1 protein of influenza B virus: NS1 binds only human and non-human primate ubiquitin-like ISG15 proteins. J Biol Chem. 2010;285(11):7852–6. Epub 2010/01/23. doi: 10.1074/jbc.C109.095703 20093371; PubMed Central PMCID: PMC2832935.

51. Versteeg GA, Hale BG, van Boheemen S, Wolff T, Lenschow DJ, Garcia-Sastre A. Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein. J Virol. 2010;84:5423–30. Epub 2010/03/12. doi: 10.1128/JVI.02395-09 20219937.

52. Pattyn E, Verhee A, Uyttendaele I, Piessevaux J, Timmerman E, Gevaert K, et al. HyperISGylation of Old World monkey ISG15 in human cells. PLoS One. 2008;3:e2427. Epub 2008/06/19. doi: 10.1371/journal.pone.0002427 18560560.

53. Basters A, Geurink PP, Rocker A, Witting KF, Tadayon R, Hess S, et al. Structural basis of the specificity of USP18 toward ISG15. Nat Struct Mol Biol. 2017;24:270–8. Epub 2017/02/07. doi: 10.1038/nsmb.3371 28165509.

54. Basters A, Knobeloch K-P, Fritz G. How USP18 deals with ISG15-modified proteins: structural basis for the specificity of the protease. The FEBS journal. 2018;285:1024–9. doi: 10.1111/febs.14260 28881486.

55. Bente DA, Alimonti JB, Shieh WJ, Camus G, Stroher U, Zaki S, et al. Pathogenesis and immune response of Crimean-Congo hemorrhagic fever virus in a STAT-1 knockout mouse model. J Virol. 2010;84(21):11089–100. Epub 2010/08/27. doi: 10.1128/JVI.01383-10 20739514; PubMed Central PMCID: PMC2953203.

56. Zivcec M, Safronetz D, Scott D, Robertson S, Ebihara H, Feldmann H. Lethal Crimean-Congo hemorrhagic fever virus infection in interferon alpha/beta receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy. J Infect Dis. 2013;207(12):1909–21. Epub 2013/02/19. doi: 10.1093/infdis/jit061 23417661; PubMed Central PMCID: PMC3654741.

57. Haddock E, Feldmann F, Hawman DW, Zivcec M, Hanley PW, Saturday G, et al. A cynomolgus macaque model for Crimean-Congo haemorrhagic fever. Nat Microbiol. 2018;3(5):556–62. Epub 2018/04/11. doi: 10.1038/s41564-018-0141-7 29632370.

58. Gill SC, von Hippel PH. Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem. 1989;182(2):319–26. Epub 1989/11/01. doi: 10.1016/0003-2697(89)90602-7 2610349.

59. Wilkinson KD, Gan-Erdene T, Kolli N. Derivitization of the C-terminus of ubiquitin and ubiquitin-like proteins using intein chemistry: methods and uses. Methods Enzymol. 2005;399:37–51. Epub 2005/12/13. doi: 10.1016/S0076-6879(05)99003-4 16338347.

60. Otwinowski Z, Minor W. Processing of X-ray Diffraction Data Collected in Oscillation Mode. C.W. Carter J, Sweet RM, editors. New York: Academic Press; 1997. 307–26 p.

61. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, et al. Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 4):235–42. Epub 2011/04/05. doi: 10.1107/S0907444910045749 21460441; PubMed Central PMCID: PMC3069738.

62. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. J Appl Crystallogr. 2007;40(Pt 4):658–74. Epub 2007/08/01. doi: 10.1107/S0021889807021206 19461840; PubMed Central PMCID: PMC2483472.

63. Webb B, Sali A. Comparative Protein Structure Modeling Using MODELLER. Curr Protoc Protein Sci. 2016;86:2 9 1–2 9 37. Epub 2016/11/02. doi: 10.1002/cpps.20 27801516.

64. Terwilliger TC, Grosse-Kunstleve RW, Afonine PV, Moriarty NW, Zwart PH, Hung L-W, et al. Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallographica Section D. 2008;64(1):61–9. doi: 10.1107/S090744490705024X 18094468

65. Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallographica Section D. 2004;60(12):2126–32. doi: 10.1107/S0907444904019158 15572765

66. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr. 2010;66(Pt 2):213–21. Epub 2010/02/04. doi: 10.1107/S0907444909052925 20124702; PubMed Central PMCID: PMC2815670.

67. Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004;60(Pt 12 Pt 1):2126–32. Epub 2004/12/02. doi: 10.1107/S0907444904019158 15572765.

68. Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J, et al. A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res. 2010;38(Web Server issue):W695–9. Epub 2010/05/05. doi: 10.1093/nar/gkq313 20439314; PubMed Central PMCID: PMC2896090.

69. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7:539. Epub 2011/10/13. doi: 10.1038/msb.2011.75 21988835; PubMed Central PMCID: PMC3261699.

70. Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 2014;42(Web Server issue):W320–4. Epub 2014/04/23. doi: 10.1093/nar/gku316 24753421; PubMed Central PMCID: PMC4086106.

71. Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983;22(12):2577–637. Epub 1983/12/01. doi: 10.1002/bip.360221211 6667333.


Článek vyšel v časopise

PLOS One


2019 Číslo 12
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

KOST
Koncepce osteologické péče pro gynekology a praktické lékaře
nový kurz
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Svět praktické medicíny 5/2023 (znalostní test z časopisu)

Imunopatologie? … a co my s tím???
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#