Epstein-barr viral BNLF2a protein hijacks the tail-anchored protein insertion machinery to block antigen processing by the transport complex TAP

Agnes I. Wycisk, Jiacheng Lin, Sandra Loch, Kathleen Hobohm, Jessica Funke, Ralph Wieneke, Joachim Koch, William R. Skach, Peter U. Mayerhofer, Robert Tampé

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Virus-infected cells are eliminated by cytotoxic T lymphocytes, which recognize viral epitopes displayed on major histocompatibility complex class I molecules at the cell surface. Herpesviruses have evolved sophisticated strategies to escape this immune surveillance. During the lytic phase of EBV infection, the viral factor BNLF2a interferes with antigen processing by preventing peptide loading of major histocompatibility complex class I molecules. Here we reveal details of the inhibition mechanism of this EBV protein.Wedemonstrate that BNLF2a acts as a tail-anchored protein, exploiting the mammalian Asna-1/WRB (Get3/Get1) machinery for posttranslational insertion into the endoplasmic reticulum membrane, where it subsequently blocks antigen translocation by the transporter associated with antigen processing (TAP). BNLF2a binds directly to the core TAP complex arresting the ATP-binding cassette transporter in a transport-incompetent conformation. The inhibition mechanism of EBV BNLF2a is distinct and mutually exclusive of other viral TAP inhibitors.

Original languageEnglish (US)
Pages (from-to)41402-41412
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number48
DOIs
StatePublished - Dec 2 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Wycisk, A. I., Lin, J., Loch, S., Hobohm, K., Funke, J., Wieneke, R., Koch, J., Skach, W. R., Mayerhofer, P. U., & Tampé, R. (2011). Epstein-barr viral BNLF2a protein hijacks the tail-anchored protein insertion machinery to block antigen processing by the transport complex TAP. Journal of Biological Chemistry, 286(48), 41402-41412. https://doi.org/10.1074/jbc.M111.237784