4I0P

HLA-DO in complex with HLA-DM

Replaces:  3USA

Summary for 4I0P

• Entry DOI: 10.2210/pdb4i0p/pdb
• Descriptor: HLA-DMA protein, HLA class II histocompatibility antigen, DM beta chain, HLA class II histocompatibility antigen, DO alpha chain, ... (9 entities in total)
• Functional Keywords: hla-dm, hla-do, hla-dr, peptide loading, immune system, inhibitor, enzyme hla-dm
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 172079.93

Authors

Guce, A.I.,Mortimer, S.E.,Stern, L.J. (deposition date: 2012-11-18, release date: 2012-12-26, Last modification date: 2024-11-27)

Primary citation

Guce, A.I.,Mortimer, S.E.,Yoon, T.,Painter, C.A.,Jiang, W.,Mellins, E.D.,Stern, L.J.
HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism.
Nat.Struct.Mol.Biol., 20:90-98, 2013

PubMed Abstract: Mammalian class II major histocompatibility (MHCII) proteins bind peptide antigens in endosomal compartments of antigen-presenting cells. The nonclassical MHCII protein HLA-DM chaperones peptide-free MHCII, protecting it against inactivation, and catalyzes peptide exchange on loaded MHCII. Another nonclassical MHCII protein, HLA-DO, binds HLA-DM and influences the repertoire of peptides presented by MHCII proteins. However, the mechanism by which HLA-DO functions is unclear. Here we have used X-ray crystallography, enzyme kinetics and mutagenesis approaches to investigate human HLA-DO structure and function. In complex with HLA-DM, HLA-DO adopts a classical MHCII structure, with alterations near the α subunit's 3₁₀ helix. HLA-DO binds to HLA-DM at the same sites implicated in MHCII interaction, and kinetic analysis showed that HLA-DO acts as a competitive inhibitor. These results show that HLA-DO inhibits HLA-DM function by acting as a substrate mimic, and the findings also limit the possible functional roles for HLA-DO in antigen presentation.

PubMed: 23222639
DOI: 10.1038/nsmb.2460

Experimental method

X-RAY DIFFRACTION (3.2 Å)