TY  - JOUR
A1  - Loch, Sandra
A1  - Klauschies, Florian
A1  - Schölz, Christian
A1  - Verweij, Marieke C.
A1  - Wiertz, Emmanuel J. H. J.
A1  - Koch, Joachim
A1  - Tampé, Robert
T1  - Signaling of a varicelloviral factor across the endoplasmic reticulum membrane induces destruction of the peptide-loading complex and immune evasion
T2  - Journal of biological chemistry
N2  - Cytotoxic T lymphocytes eliminate infected cells upon surface display of antigenic peptides on major histocompatibility complex I molecules. To promote immune evasion, UL49.5 of several varicelloviruses interferes with the pathway of major histocompatibility complex I antigen processing. However, the inhibition mechanism has not been elucidated yet. Within the macromolecular peptide-loading complex we identified the transporter associated with antigen processing (TAP1 and TAP2) as the prime target of UL49.5. Moreover, we determined the active oligomeric state and crucial elements of the viral factor. Remarkably, the last two residues of the cytosolic tail of UL49.5 are essential for endoplasmic reticulum (ER)-associated proteasomal degradation of TAP. However, this process strictly requires additional signaling of an upstream regulatory element in the ER lumenal domain of UL49.5. Within this new immune evasion mechanism, we show for the first time that additive elements of a small viral factor and their signaling across the ER membrane are essential for targeted degradation of a multi-subunit membrane complex.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76349
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-763498
SN  - 0021-9258
VL  - 283.2008
IS  - 19
SP  - 13428
EP  - 13436
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -