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

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.