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4i0p

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Revision as of 02:10, 25 December 2014

HLA-DO in complex with HLA-DM

Structural highlights

4i0p is a 8 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3usa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	3108, HLA-DMA (Homo sapiens), 3109, DMB, HLA-DMB, RING7 (Homo sapiens), 3111, HLA-DNA, HLA-DOA, HLA-DZA (Homo sapiens), 3112, HLA-DOB (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Weber DA, Evavold BD, Jensen PE. Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM. Science. 1996 Oct 25;274(5287):618-20. PMID:8849454
↑ Mosyak L, Zaller DM, Wiley DC. The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation. Immunity. 1998 Sep;9(3):377-83. PMID:9768757
↑ Nicholson MJ, Moradi B, Seth NP, Xing X, Cuny GD, Stein RL, Wucherpfennig KW. Small molecules that enhance the catalytic efficiency of HLA-DM. J Immunol. 2006 Apr 1;176(7):4208-20. PMID:16547258
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4i0p"

@@ Line 7: / Line 7: @@
 <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://www.rcsb.org/pdb/explore.do?structureId=4i0p RCSB], [http://www.ebi.ac.uk/pdbsum/4i0p PDBsum]</span></td></tr>
 </table>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4i0p

From Proteopedia

Revision as of 02:10, 25 December 2014

HLA-DO in complex with HLA-DM

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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