University of Surrey

Test tubes in the lab Research in the ATI Dance Research

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.

Full text not available from this repository.

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 :
NameEmailORCID
Wycisk, AIUNSPECIFIEDUNSPECIFIED
Lin, JUNSPECIFIEDUNSPECIFIED
Loch, SUNSPECIFIEDUNSPECIFIED
Hobohm, KUNSPECIFIEDUNSPECIFIED
Funke, JUNSPECIFIEDUNSPECIFIED
Wieneke, RUNSPECIFIEDUNSPECIFIED
Koch, JUNSPECIFIEDUNSPECIFIED
Skach, WRUNSPECIFIEDUNSPECIFIED
Mayerhofer, PUp.mayerhofer@surrey.ac.ukUNSPECIFIED
Tampé, RUNSPECIFIEDUNSPECIFIED
Date : 2011
Identification Number : https://doi.org/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 :
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

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800