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

Wycisk, AI, Lin, J, Loch, S, Hobohm, K, Funke, J, Wieneke, R, Koch, J, Skach, WR, Mayerhofer, PU and Tampé, R (2011) Epstein-Barr viral BNLF2a protein hijacks the tail-anchored protein insertion machinery to block antigen processing by the transport complex TAP J Biol Chem, 286. pp. 41402-41412.

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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. We demonstrate 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.

Item Type:	Article
Authors :	Name Email ORCID Wycisk, AI Lin, J Loch, S Hobohm, K Funke, J Wieneke, R Koch, J Skach, WR Mayerhofer, PU p.mayerhofer@surrey.ac.uk Tampé, R
Date :	2011
Identification Number :	10.1074/jbc.M111.237784
Uncontrolled Keywords :	ATP-Binding Cassette Transporters/genetics/*metabolism Animals Antigen Presentation/genetics Arsenite Transporting ATPases/genetics/metabolism Endoplasmic Reticulum/genetics/metabolism/virology Epstein-Barr Virus Infections/genetics/*metabolism HeLa Cells Herpesvirus 4, Human/genetics/*metabolism Histocompatibility Antigens Class I/genetics/*metabolism Humans Multiprotein Complexes/genetics/*metabolism Nuclear Proteins/genetics/metabolism Spodoptera Viral Matrix Proteins/genetics/*metabolism
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 10:42
Last Modified :	17 May 2017 14:51
URI:	http://epubs.surrey.ac.uk/id/eprint/828849

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