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Science. 2017 Nov 24;358(6366):1060-1064. doi: 10.1126/science.aao6001. Epub 2017 Oct 12.

Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing.

Author information

1
Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue Strasse 9, 60438 Frankfurt/Main, Germany. c.thomas@em.uni-frankfurt.de tampe@em.uni-frankfurt.de.
2
Cluster of Excellence-Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue Strasse 9, 60438 Frankfurt/Main, Germany.

Abstract

Adaptive immunity is shaped by a selection of peptides presented on major histocompatibility complex class I (MHC I) molecules. The chaperones Tapasin (Tsn) and TAP-binding protein-related (TAPBPR) facilitate MHC I peptide loading and high-affinity epitope selection. Despite the pivotal role of Tsn and TAPBPR in controlling the hierarchical immune response, their catalytic mechanism remains unknown. Here, we present the x-ray structure of the TAPBPR-MHC I complex, which delineates the central step of catalysis. TAPBPR functions as peptide selector by remodeling the MHC I α2-1-helix region, stabilizing the empty binding groove, and inserting a loop into the groove that interferes with peptide binding. The complex explains how mutations in MHC I-specific chaperones cause defects in antigen processing and suggests a unifying mechanism of peptide proofreading.

PMID:
29025996
DOI:
10.1126/science.aao6001
[Indexed for MEDLINE]

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