TY  - JOUR
A1  - Koch, Joachim
A1  - Guntrum, Renate
A1  - Heintke, Susanne
A1  - Kyritsis, Christoph
A1  - Tampé, Robert
T1  - Functional dissection of the transmembrane domains of the transporter associated with antigen processing (TAP)
T2  - Journal of biological chemistry
N2  - The transporter associated with antigen processing (TAP1/2) translocates cytosolic peptides of proteasomal degradation into the endoplasmic reticulum (ER) lumen. A peptide-loading complex of tapasin, major histocompatibility complex class I, and several auxiliary factors is assembled at the transporter to optimize antigen display to cytotoxic T-lymphocytes at the cell surface. The heterodimeric TAP complex has unique N-terminal domains in addition to a 6 + 6-transmembrane segment core common to most ABC transporters. Here we provide direct evidence that this core TAP complex is sufficient for (i) ER targeting, (ii) heterodimeric assembly within the ER membrane, (iii) peptide binding, (iv) peptide transport, and (v) specific inhibition by the herpes simplex virus protein ICP47 and the human cytomegalovirus protein US6. We show for the first time that the translocation pore of the transporter is composed of the predicted TM-(5-10) of TAP1 and TM-(4-9) of TAP2. Moreover, we demonstrate that the N-terminal domains of TAP1 and TAP2 are essential for recruitment of tapasin, consequently mediating assembly of the macromolecular peptide-loading complex.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76147
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-761475
SN  - 0021-9258
VL  - 279
IS  - 11
SP  - 10142
EP  - 10147
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -