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Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a receptive conformation.

ABSTRACT: The recognition of virus infected or malignantly transformed cells by cytotoxic T lymphocytes critically depends on the transporter associated with antigen processing (TAP), which delivers proteasomal degradation products into the endoplasmic reticulum lumen for subsequent loading of major histocompatibility complex class I molecules. Here we have identified a single cysteinyl residue in the TAP complex that modulates peptide binding and translocation, thereby restricting the epitope repertoire. Cysteine 213 in human TAP2 was found to be part of a newly uncovered substrate-binding site crucial for peptide recognition. This residue contacts the peptide in the binding pocket in an orientated manner. The translocation complex can be reversibly inactivated by thiol modification of this cysteinyl residue. As part of an unexpected mechanism, this residue is crucial in complementing the binding pocket for a given subset of epitopes as well as in maintaining a substrate-receptive conformation of the translocation complex.

SUBMITTER: Baldauf C

PROVIDER: S-EPMC2889111 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a receptive conformation.

Baldauf Christoph C Schrodt Susanne S Herget Meike M Koch Joachim J Tampé Robert R

Proceedings of the National Academy of Sciences of the United States of America 20100503 20

The recognition of virus infected or malignantly transformed cells by cytotoxic T lymphocytes critically depends on the transporter associated with antigen processing (TAP), which delivers proteasomal degradation products into the endoplasmic reticulum lumen for subsequent loading of major histocompatibility complex class I molecules. Here we have identified a single cysteinyl residue in the TAP complex that modulates peptide binding and translocation, thereby restricting the epitope repertoire. ...[more]

PMID: 20439763

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Dataset Information

Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a receptive conformation.

Publications

Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a receptive conformation.

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