6B9K

Solution NMR Structure of Unbound P18-I10

Summary for 6B9K

• Entry DOI: 10.2210/pdb6b9k/pdb
• NMR Information: BMRB: 30350
• Descriptor: ARG-GLY-PRO-GLY-ARG-ALA-PHE-VAL-THR-ILE (1 entity in total)
• Functional Keywords: structure from cyana 2.1, peptide binding protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 1075.27

Authors

Flores-Solis, D.,McShan, A.,Sgourakis, N. (deposition date: 2017-10-10, release date: 2018-07-25, Last modification date: 2024-05-15)

Primary citation

McShan, A.C.,Natarajan, K.,Kumirov, V.K.,Flores-Solis, D.,Jiang, J.,Badstubner, M.,Toor, J.S.,Bagshaw, C.R.,Kovrigin, E.L.,Margulies, D.H.,Sgourakis, N.G.
Peptide exchange on MHC-I by TAPBPR is driven by a negative allostery release cycle.
Nat. Chem. Biol., 14:811-820, 2018

PubMed Abstract: 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.

PubMed: 29988068
DOI: 10.1038/s41589-018-0096-2

Experimental method

SOLUTION NMR