GSBS Student Publications

Student Author(s)

Corrie A. Painter; Maria P. Negroni

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

2011-11-29

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Department of Pathology

Document Type

Article

Disciplines

Biochemistry, Biophysics, and Structural Biology | Chemistry | Life Sciences | Medicine and Health Sciences | Physical Sciences and Mathematics

Abstract

HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of αF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide-binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the α-subunit 3(10) helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange.

Rights and Permissions

This article is freely available online through the PNAS open access option.

DOI of Published Version

10.1073/pnas.1108074108

Source

Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19329-34. Link to article on publisher's website

Journal/Book/Conference Title

PNAS

Related Resources

Link to article in PubMed

PubMed ID

22084083

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