4I0P: HLA-DO in complex with HLA-DM

Citation:
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 alpha subunit's 3(1)(0) 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.
PDB ID: 4I0PDownload
MMDB ID: 106257
PDB Deposition Date: 2012/11/18
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4I0P: tetrameric; determined by author and by software (PISA)
Molecular Components in 4I0P
Label Count Molecule
Proteins (4 molecules)
1
Hla-dma Protein
Molecule annotation
1
HLA Class II Histocompatibility Antigen, DM Beta Chain(Gene symbol: HLA-DMB)
Molecule annotation
1
HLA Class II Histocompatibility Antigen, DO Alpha Chain(Gene symbol: HLA-DOA)
Molecule annotation
1
HLA Class II Histocompatibility Antigen, DO Beta Chain(Gene symbol: HLA-DOB)
Molecule annotation
Chemicals (6 molecules)
1
3
2
1
3
1
4
1
Molecule information is not avaliable.
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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