TY  - JOUR
A1  - Schrodt, Susanne
A1  - Koch, Joachim
A1  - Tampé, Robert
T1  - Membrane topology of the transporter associated with antigen processing (TAP1) within an assembled functional peptide-loading complex
T2  - Journal of biological chemistry
N2  - The transporter associated with antigen processing (TAP) translocates antigenic peptides from the cytosol into the endoplasmic reticular lumen for subsequent loading onto major histocompatibility complex (MHC) class I molecules. These peptide-MHC complexes are inspected at the cell surface by cytotoxic T-lymphocytes. Assembly of the functional peptide transport and loading complex depends on intra- and intermolecular packing of transmembrane helices (TMs). Here, we have examined the membrane topology of human TAP1 within an assembled and functional transport complex by cysteine-scanning mutagenesis. The accessibility of single cysteine residues facing the cytosol or endoplasmic reticular lumen was probed by a minimally invasive approach using membrane-impermeable, thiol-specific fluorophores in semipermeabilized “living” cells. TAP1 contains ten transmembrane segments, which place the N and C termini in the cytosol. The transmembrane domain consists of a translocation core of six TMs, a building block conserved among most ATP-binding cassette transporters, and a unique additional N-terminal domain of four TMs, essential for tapasin binding and assembly of the peptide-loading complex. This study provides a first map of the structural organization of the TAP machinery within the macromolecular MHCI peptide-loading complex.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76234
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762349
SN  - 0021-9258
VL  - 281
IS  - 10
SP  - 6455
EP  - 6462
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -