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| | ==HLA-DO in complex with HLA-DM== | | ==HLA-DO in complex with HLA-DM== |
| - | <StructureSection load='4i0p' size='340' side='right' caption='[[4i0p]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='4i0p' size='340' side='right'caption='[[4i0p]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i0p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3usa 3usa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I0P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i0p]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3usa 3usa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I0P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3108, HLA-DMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 3109, DMB, HLA-DMB, RING7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 3111, HLA-DNA, HLA-DOA, HLA-DZA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), 3112, HLA-DOB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i0p OCA], [https://pdbe.org/4i0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i0p RCSB], [https://www.ebi.ac.uk/pdbsum/4i0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i0p ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i0p OCA], [http://pdbe.org/4i0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i0p RCSB], [http://www.ebi.ac.uk/pdbsum/4i0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i0p ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DOB_HUMAN 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. [[http://www.uniprot.org/uniprot/DOA_HUMAN 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. [[http://www.uniprot.org/uniprot/DMB_HUMAN 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.<ref>PMID:8849454</ref> <ref>PMID:9768757</ref> <ref>PMID:16547258</ref> | + | [https://www.uniprot.org/uniprot/Q6ICR9_HUMAN Q6ICR9_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Guce, A I]] | + | [[Category: Large Structures]] |
| - | [[Category: Mortimer, S E]] | + | [[Category: Guce AI]] |
| - | [[Category: Stern, L J]] | + | [[Category: Mortimer SE]] |
| - | [[Category: Enzyme hla-dm]] | + | [[Category: Stern LJ]] |
| - | [[Category: Hla-dm]]
| + | |
| - | [[Category: Hla-do]]
| + | |
| - | [[Category: Hla-dr]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Peptide loading]]
| + | |
| Structural highlights
Function
Q6ICR9_HUMAN
Publication Abstract from PubMed
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(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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guce AI, Mortimer SE, Yoon T, Painter CA, Jiang W, Mellins ED, Stern LJ. HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism. Nat Struct Mol Biol. 2012 Dec 9. doi: 10.1038/nsmb.2460. PMID:23222639 doi:http://dx.doi.org/10.1038/nsmb.2460
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