4FQX

Crystal structure of HLA-DM bound to HLA-DR1

Summary for 4FQX

• Entry DOI: 10.2210/pdb4fqx/pdb
• Descriptor: HLA class II histocompatibility antigen, DM alpha chain, HLA class II histocompatibility antigen, DM beta chain, Synthetic peptide, ... (7 entities in total)
• Functional Keywords: immune complex, peptide loading, peptide editing, antigen presentation, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 92704.32

Authors

Sethi, D.K.,Pos, W.,Wucherpfennig, K.W. (deposition date: 2012-06-25, release date: 2013-01-09, Last modification date: 2024-11-06)

Primary citation

Pos, W.,Sethi, D.K.,Call, M.J.,Schulze, M.S.,Anders, A.K.,Pyrdol, J.,Wucherpfennig, K.W.
Crystal Structure of the HLA-DM-HLA-DR1 Complex Defines Mechanisms for Rapid Peptide Selection.
Cell(Cambridge,Mass.), 151:1557-1568, 2012

PubMed Abstract: HLA-DR molecules bind microbial peptides in an endosomal compartment and present them on the cell surface for CD4 T cell surveillance. HLA-DM plays a critical role in the endosomal peptide selection process. The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove. Flipping of a tryptophan away from the HLA-DR1 P1 pocket enables major conformational changes that position hydrophobic HLA-DR residues into the P1 pocket. These conformational changes accelerate peptide dissociation and stabilize the empty HLA-DR peptide-binding groove. Initially, incoming peptides have access to only part of the HLA-DR groove and need to compete with HLA-DR residues for access to the P2 site and the hydrophobic P1 pocket. This energetic barrier creates a rapid and stringent selection process for the highest-affinity binders. Insertion of peptide residues into the P2 and P1 sites reverses the conformational changes, terminating selection through DM dissociation.

PubMed: 23260142
DOI: 10.1016/j.cell.2012.11.025

Experimental method

X-RAY DIFFRACTION (2.599 Å)