TY  - JOUR
A1  - Wycisk, Agnes Isabella
A1  - Lin, Jiacheng
A1  - Loch, Sandra
A1  - Hobohm, Kathleen
A1  - Funke, Jessica
A1  - Wieneke, Ralph
A1  - Koch, Joachim
A1  - Skach, William R.
A1  - Mayerhofer, Peter Uli
A1  - Tampé, Robert
T1  - Epstein-Barr viral BNLF2a protein hijacks the tail-anchored protein insertion machinery to block antigen processing by the transport complex TAP
T2  - Journal of biological chemistry
N2  - 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.
KW  - ABC Transporter
KW  - Antigen Processing
KW  - Cellular Immune Response
KW  - Intracellular Trafficking
KW  - Viral Immunology
KW  - Get Pathway
KW  - Tail-anchored Proteins
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76558
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-765586
SN  - 0021-9258
VL  - 286.2011
IS  - 48
SP  - 41402
EP  - 41412
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -