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| | ==Crystal structure of disulfide-linked HLA-G dimer== | | ==Crystal structure of disulfide-linked HLA-G dimer== |
| - | <StructureSection load='2d31' size='340' side='right' caption='[[2d31]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='2d31' size='340' side='right'caption='[[2d31]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2d31]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2D31 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2d31]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2D31 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2d31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d31 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2d31 RCSB], [http://www.ebi.ac.uk/pdbsum/2d31 PDBsum]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <table>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2d31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d31 OCA], [https://pdbe.org/2d31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2d31 RCSB], [https://www.ebi.ac.uk/pdbsum/2d31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2d31 ProSAT]</span></td></tr> |
| - | == Disease ==
| + | </table> |
| - | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | + | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HLAG_HUMAN HLAG_HUMAN]] Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells. [[http://www.uniprot.org/uniprot/H2AX_HUMAN H2AX_HUMAN]] Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation.<ref>PMID:10959836</ref> <ref>PMID:12419185</ref> <ref>PMID:12607005</ref> <ref>PMID:15201865</ref> [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [https://www.uniprot.org/uniprot/HLAG_HUMAN HLAG_HUMAN] Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d3/2d31_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d3/2d31_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2d31 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2d31" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| - | *[[Major histocompatibility complex|Major histocompatibility complex]] | + | *[[MHC 3D structures|MHC 3D structures]] |
| | + | *[[MHC I 3D structures|MHC I 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Arase, H.]] | + | [[Category: Large Structures]] |
| - | [[Category: Kohda, D.]] | + | [[Category: Arase H]] |
| - | [[Category: Kumagai, I.]] | + | [[Category: Kohda D]] |
| - | [[Category: Kuroki, K.]] | + | [[Category: Kumagai I]] |
| - | [[Category: Maenaka, K.]] | + | [[Category: Kuroki K]] |
| - | [[Category: Ose, T.]] | + | [[Category: Maenaka K]] |
| - | [[Category: Rasubala, L.]] | + | [[Category: Ose T]] |
| - | [[Category: Shiratori, I.]] | + | [[Category: Rasubala L]] |
| - | [[Category: Shiroishi, M.]] | + | [[Category: Shiratori I]] |
| - | [[Category: Tsumoto, K.]] | + | [[Category: Shiroishi M]] |
| - | [[Category: Immune system-cell cycle complex]]
| + | [[Category: Tsumoto K]] |
| - | [[Category: Mhc class i]]
| + | |
| Structural highlights
Function
HLAG_HUMAN Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
HLA-G is a nonclassical major histocompatibility complex class I (MHCI) molecule, which is expressed in trophoblasts and confers immunological tolerance in the maternal-fetal interface by binding to leukocyte Ig-like receptors (LILRs, also called as LIR/ILT/CD85) and CD8. HLA-G is expressed in disulfide-linked dimer form both in solution and at the cell surface. Interestingly, MHCI dimer formations have been involved in pathogenesis and T cell activation. The structure and receptor binding characteristics of MHCI dimers have never been evaluated. Here we performed binding studies showing that the HLA-G dimer exhibited higher overall affinity to LILRB1/2 than the monomer by significant avidity effects. Furthermore, the cell reporter assay demonstrated that the dimer formation remarkably enhanced the LILRB1-mediated signaling at the cellular level. We further determined the crystal structure of the wild-type dimer of HLA-G with the intermolecular Cys(42)-Cys(42) disulfide bond. This dimer structure showed the oblique configuration to expose two LILR/CD8-binding sites upward from the membrane easily accessible for receptors, providing plausible 1:2 (HLA-G dimer:receptors) complex models. These results indicated that the HLA-G dimer conferred increased avidity in a proper structural orientation to induce efficient LILR signaling, resulting in the dominant immunosuppressive effects. Moreover, structural and functional implications for other MHCI dimers observed in activated T cells and the pathogenic allele, HLA-B27, are discussed.
Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer.,Shiroishi M, Kuroki K, Ose T, Rasubala L, Shiratori I, Arase H, Tsumoto K, Kumagai I, Kohda D, Maenaka K J Biol Chem. 2006 Apr 14;281(15):10439-47. Epub 2006 Feb 2. PMID:16455647[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shiroishi M, Kuroki K, Ose T, Rasubala L, Shiratori I, Arase H, Tsumoto K, Kumagai I, Kohda D, Maenaka K. Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J Biol Chem. 2006 Apr 14;281(15):10439-47. Epub 2006 Feb 2. PMID:16455647 doi:10.1074/jbc.M512305200
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