A structural model of pestivirus E(rns) based on disulfide bond connectivity and homology modeling reveals an extremely rare vicinal disulfide

J.P.M. Langedijk, P.A. van Veelen, W.M.M. Schaaper, A.H. de Ru, R.H. Meloen, M.M. Hulst

    Research output: Contribution to journalArticleAcademicpeer-review

    30 Citations (Scopus)

    Abstract

    Erns is a pestivirus envelope glycoprotein and is the only known viral surface protein with RNase activity. Erns is a disulfide-linked homodimer of 100 kDa; it is found on the surface of pestivirus-infected cells and is secreted into the medium. In this study, the disulfide arrangement of the nine cysteines present in the mature dimer was established by analysis of the proteolytically cleaved protein. Fragments were obtained after digestion with multiple proteolytic enzymes and subsequently analyzed by liquid chromatography-electrospray ionization mass spectrometry. The analysis demonstrates which cysteine is involved in dimerization and reveals an extremely rare vicinal disulfide bridge of unknown function. With the assistance of the disulfide arrangement, a three-dimensional model was built by homology modeling based on the alignment with members of the Rh/T2/S RNase family. Compared to these other RNase family members, Erns shows an N-terminal truncation, a large insertion of a cystine-rich region, and a C-terminal extension responsible for membrane translocation. The homology to mammalian RNase 6 supports a possible role of Erns in B-cell depletion.
    Original languageEnglish
    Pages (from-to)10383-10392
    JournalJournal of Virology
    Volume76
    DOIs
    Publication statusPublished - 2002

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