3QXD: F54c Hla-dr1 Bound With Clip Peptide

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 alphaF54, 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 alpha-subunit 3(10) helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange.
PDB ID: 3QXDDownload
MMDB ID: 95041
PDB Deposition Date: 2011/3/1
Updated in MMDB: 2011/12 
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 3QXD: trimeric; determined by author and by software (PISA)
Molecular Components in 3QXD
Label Count Molecule
Proteins (3 molecules)
HLA Class II Histocompatibility Antigen, DR Alpha Chain
Molecule annotation
HLA Class II Histocompatibility Antigen, Drb1-1 Beta Chain
Molecule annotation
HLA Class II Histocompatibility Antigen Gamma Chain Peptide
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB