3QXD

F54C HLA-DR1 bound with CLIP peptide

Summary for 3QXD

• Entry DOI: 10.2210/pdb3qxd/pdb
• Related: 3QXA
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-1 beta chain, HLA class II histocompatibility antigen gamma chain peptide, ... (4 entities in total)
• Functional Keywords: mhc class ii, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903 P04229; Cell membrane; Single-pass type II membrane protein (Potential): P04233
• Total number of polymer chains: 6
• Total formula weight: 89737.31

Authors

Painter, C.A.,Stern, L.J. (deposition date: 2011-03-01, release date: 2011-11-16, Last modification date: 2024-10-30)

Primary citation

Painter, C.A.,Negroni, M.P.,Kellersberger, K.A.,Zavala-Ruiz, Z.,Evans, J.E.,Stern, L.J.
Conformational lability in the class II MHC 310 helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange.
Proc.Natl.Acad.Sci.USA, 108:19329-19334, 2011

PubMed 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.

PubMed: 22084083
DOI: 10.1073/pnas.1108074108

Experimental method

X-RAY DIFFRACTION (2.302 Å)