4i0p
From Proteopedia
HLA-DO in complex with HLA-DM
Structural highlights
Function[DOB_HUMAN] Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells. Modifies peptide exchange activity of HLA-DM. [DOA_HUMAN] Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells. Modifies peptide exchange activity of HLA-DM. [DMB_HUMAN] Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO.[1] [2] [3] Publication Abstract from PubMedMammalian 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(10) 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. HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism.,Guce AI, Mortimer SE, Yoon T, Painter CA, Jiang W, Mellins ED, Stern LJ Nat Struct Mol Biol. 2012 Dec 9. doi: 10.1038/nsmb.2460. PMID:23222639[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Guce, A I | Mortimer, S E | Stern, L J | Enzyme hla-dm | Hla-dm | Hla-do | Hla-dr | Immune system | Inhibitor | Peptide loading
