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Publication Abstract from PubMed

Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy. Incoming peptides are recognized according to the global stability of the final pMHC-I product and anneal in a native-like conformation to be edited by TAPBPR. Our results demonstrate an inverse relationship between MHC-I peptide occupancy and TAPBPR binding affinity, wherein the lifetime and structural features of transiently bound peptides control the regulation of a conformational switch located near the TAPBPR binding site, which triggers TAPBPR release. These results suggest a similar mechanism for the function of tapasin in the peptide-loading complex.

Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.,McShan AC, Natarajan K, Kumirov VK, Flores-Solis D, Jiang J, Badstubner M, Toor JS, Bagshaw CR, Kovrigin EL, Margulies DH, Sgourakis NG Nat Chem Biol. 2018 Jul 9. pii: 10.1038/s41589-018-0096-2. doi:, 10.1038/s41589-018-0096-2. PMID:29988068^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.