Archives of Virology

, Volume 164, Issue 4, pp 961–969 | Cite as

Identification and characterization of novel double zinc fingers encoded by putative proteins in genome of white spot syndrome virus

  • Malathi ShekarEmail author
  • Moleyur Nagarajappa Venugopal
Original Article


White spot syndrome virus (WSSV), is a major viral pathogen affecting the shrimp culture industry worldwide. Studies in understanding the mechanisms of WSSV pathogenicity has led to the identification of The Really Interesting New Gene (RING) finger domains in WSSV encoded proteins that have been shown to function as E3 ligase modulating the host-ubiquitin pathway. In this study, we report two proteins encoded by the WSSV genome to harbor a double zinc finger domain, one each in its N- and C-terminal region. Sequence and structural analysis of the two domains showed the N- and C-terminal domains to be similar to known RING1 and RING2 domains of eukaryotic RBR (RING-between-RING) ligases respectively. This is the first report wherein genes within WSSV are shown to encode for double RING domains, which could pave way in understanding further, the function of these proteins and their role in the pathogenic mechanisms of the virus.



The authors acknowledge the funding support received from the BTISnet Program (BT/BI 04/049/99/), Department of Biotechnology, Government of India, NewDelhi.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest

Ethical approval

This article does not contain any human or animal studies.


  1. 1.
    Banks L, Pim D, Thomas M (2003) Viruses and the 26S proteasome: hacking into destruction. Trends Biochem Sci 28:452–459CrossRefPubMedGoogle Scholar
  2. 2.
    Benkert P, Schwede T, Tosatto SCE (2009) QMEANclust: estimation of protein model quality by combining a composite scoring function with structural density information. BMC Struct Biol 9:35CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Borden KLB, Freemont PS (1996) The RING finger domain: a recent example of a sequence-structure family. Curr Opin Struct Biol 6:395–401CrossRefPubMedGoogle Scholar
  4. 4.
    Ciechanover A, Schwartz AL (1998) The ubiquitin-proteasome pathway: The complexity and myriad functions of proteins death. Proc Natl Acad Sci USA 95:2727–2730CrossRefPubMedGoogle Scholar
  5. 5.
    deCastro E, Sigrist CJA, Gattiker A, Bulliard V, Langendijk-Genevaux PS, Gasteiger E, Bairoch A, Hulo N (2006) ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins. Nucleic Acids Res 34:W362–W365CrossRefGoogle Scholar
  6. 6.
    DeLano WL (2002) The PyMOL molecular graphics system. Delano Scientific, San Carlos Accessed 20 Apr 2015
  7. 7.
    Deshaies RJ, Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434CrossRefGoogle Scholar
  8. 8.
    Duda DM, Olszewski JL, Schuermann JP, Kurinov I, Miller DJ, Nourse A, Alpi AF, Schulman BA (2013) Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an ariadne-family E3 and insights into ligation mechanism. Structure 21:1030–1041CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    George AJ, Hoffiz YC, Charles AJ, Zhu Y, Mabb AM (2018) A comprehensive atlas of E3 ubiquitin ligase mutations in neurological disorders. Front Genet 9:29. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    He F, Fenner BJ, Godwin AK, Kwang J (2006) White spot syndrome virus open reading frame 222 encodes a viral E3 ligase and mediates degradation of a host tumor suppressor via ubiquitination. J Virol 80:3884–3892CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    He F, Kwang J (2008) Identification and characterization of a new E3 ubiquitin ligase in white spot syndrome virus involved in virus latency. Virol J 5:151–158CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jeena K, Prasad PK, Pathan MK, Babu GP (2012) Expression profiling of WSSV ORF 199 and shrimp ubiquitin conjugating enzyme in WSSV Infected Penaeus monodon. Asian Aust J Anim Sci 25:1184–1189CrossRefGoogle Scholar
  13. 13.
    Kosarev P, Mayer KF, Hardtke CS (2002) Evaluation and classification of RING-finger domains encoded by the Arabidopsis genome. Genome Biol 3:RESEARCH0016CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Krishna SS, Majumdar I, Grishin NV (2003) Structural classification of zinc fingers. Nucleic Acids Res 31:532–550CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Laity JH, Lee BM, Peter E, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11:39–46CrossRefGoogle Scholar
  16. 16.
    Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK-a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291CrossRefGoogle Scholar
  17. 17.
    Lechtenberg BC, Rajput A, Sanishvili R, Dobaczewska MK, Ware CF, Mace PD, Riedl SJ (2016) Structure of a HOIP/E2 ~ ubiquitin complex reveals RBR E3 ligase mechanism and regulation. Nature 529:546–550CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lecker SH, Goldberg AL, Mitch WE (2006) Protein degradation by the ubiquitin–proteasome pathway in normal and disease states. Am Soc Nephrol 17:1807–1818CrossRefGoogle Scholar
  19. 19.
    Lightner DV (1996) A handbook of pathology and diagnostic procedures for diseases of Penaeid shrimp. Special publication of the World Aquaculture Society, BatonRougeGoogle Scholar
  20. 20.
    Malgieri G, Palmieri M, Russo L, Fattorusso R, Pedone PV, Isernia C (2015) The prokaryotic zinc-finger: structure, function and comparison with the eukaryotic counterpart. FEBS J 282:4480–4496CrossRefPubMedGoogle Scholar
  21. 21.
    Marin I, Lucas JI, Gradilla AC, Ferrus A (2004) Parkin and relatives: the RBR family of ubiquitin ligases. Physiol Genomics 17:253–263CrossRefPubMedGoogle Scholar
  22. 22.
    Metzger MB, Pruneda JN, Klevit RE, Weissman AM (2014) RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim Biophys Acta 1843:47–60CrossRefPubMedGoogle Scholar
  23. 23.
    Pickart CM, Fushman D (2004) Polyubiquitin chains: polymeric protein signals. Curr Opin Chem Biol 8:610–616CrossRefPubMedGoogle Scholar
  24. 24.
    Ponting CP, Schultz J, Milpetz F, Bork P (1999) SMART: identification and annotation of domains from signalling and extracellular protein sequences. Nucleic Acids Res 27:229–232CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Potestio R, Aleksiev T, Pontiggia F, Cozzini S, Micheletti C (2010) ALADYN: a web server for aligning proteins by matching their large-scale motion. Nucleic Acids Res 38:W41–W45CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Shekar M, Venugopal MN (2017) Insight into a transcriptional adaptor zinc finger encoded by a putative protein in the white spot syndrome virus genome. Interdiscip Sci Comput Life Sci 22:22. CrossRefGoogle Scholar
  27. 27.
    Shekhar MS, Ponniah AG (2015) Recent insights into host–pathogen interaction in white spot syndrome virus infected penaeid shrimp. J Fish Dis 38:599–612CrossRefPubMedGoogle Scholar
  28. 28.
    Sigrist CJA, de Castro E, Cerutti L, Cuche BA, Hulo N, Bridge A, Lydie B, Xenarios I (2013) New and continuing developments at PROSITE. Nucleic Acids Res 41:D344–D347CrossRefPubMedGoogle Scholar
  29. 29.
    Smit JJ, Monteferrario D, Noordermeer SM, van Dijk WJ, van der Reijden BA, Sixma TK (2012) The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension. EMBO J 31:3833–3844CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Spratt DE, Walden H, Shaw GS (2014) RBR E3 ubiquitin ligases: new structures, new insights, new questions. Biochem J 458:421–437CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Thien CB, Walker F, Langdon WY (2001) RING finger mutations that abolish c-Cbl-directed polyubiquitination and downregulation of the EGF receptor are insufficient for cell transformation. Mol Cell 7:355–365CrossRefPubMedGoogle Scholar
  32. 32.
    van Baren MJ, van der Linde HC, Breedveld GJ, Baarends WM, Rizzu P, de Graaff E, Oostra BA, Heutink P (2002) A double RING-H2 domain in RNF32, a gene expressed during sperm formation. Biochem Biophys Res Comm 292:58–65CrossRefPubMedGoogle Scholar
  33. 33.
    van Hulten MCW, Witteveldt J, Peters S, Kloosterboer N, Tarchini R, Fiers M, Klein SH, Lankhorst R, Vlak JM (2001) The white spot syndrome virus DNA genome sequence. Virology 286:7–22CrossRefPubMedGoogle Scholar
  34. 34.
    Vlak JM, Bonami JR, Flegel TW, Kou GH, Lightner DV, Lo CF, Loh PC, Walker PW (2005) Nimaviridae. In: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (eds) Virus taxonomy. Eighth report of the international committee on taxonomy of viruses. Elsevier, Amsterdam, pp 187–192Google Scholar
  35. 35.
    Wang Z, Chua HK, Gusti AA, He F, Fenner B, Manopo I, Wang H, Kwang J (2005) RING-H2 protein WSSV249 from white spot syndrome virus sequesters a shrimp ubiquitin-conjugating enzyme, PvUbc, for viral pathogenesis. J Virol 79:8764–8772CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wenzel DM, Klevit RE (2012) Following Ariadne’s thread: a new perspective on RBR ubiquitin ligases. BMC Biol 10:24. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Yang F, He J, Lin XH, Li Q, Pan D, Zhang XB, Xu X (2001) Complete genome sequence of the shrimp white spot bacilliform virus. J Virol 75:11811–11820CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zhang Y, Li LF, Munir M, Qiu HJ (2018) RING-domain E3 ligase-mediated host–virus interactions: orchestrating immune responses by the host and antagonizing immune defense by viruses. Front Immunol 9:1083. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Malathi Shekar
    • 1
    Email author
  • Moleyur Nagarajappa Venugopal
    • 1
  1. 1.Department of Fisheries Microbiology, DBT Bioinformatics Centre, College of FisheriesKarnataka Veterinary, Animal and Fisheries Sciences UniversityMangaloreIndia

Personalised recommendations