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| - | ==EGF DOMAINS 1,2,5 OF HUMAN EMR2, A 7-TM IMMUNE SYSTEM MOLECULE, IN COMPLEX WITH CALCIUM.== | + | |
| - | <StructureSection load='2bo2' size='340' side='right' caption='[[2bo2]], [[Resolution|resolution]] 2.60Å' scene=''> | + | ==EGF Domains 1,2,5 of human EMR2, a 7-TM immune system molecule, in complex with calcium.== |
| | + | <StructureSection load='2bo2' size='340' side='right'caption='[[2bo2]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bo2]] is a 2 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=2BO2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BO2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bo2]] is a 2 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=2BO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BO2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene></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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bou|2bou]], [[2box|2box]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene></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=2bo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bo2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bo2 RCSB], [http://www.ebi.ac.uk/pdbsum/2bo2 PDBsum]</span></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=2bo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bo2 OCA], [https://pdbe.org/2bo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bo2 RCSB], [https://www.ebi.ac.uk/pdbsum/2bo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bo2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/AGRE2_HUMAN AGRE2_HUMAN] Vibratory urticaria. The disease is caused by variants affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EMR2_HUMAN EMR2_HUMAN]] Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment. Promotes granulocyte chemotaxis, degranulation and adhesion. In macrophages, promotes the release of inflammatory cytokines, including IL8 and TNF.<ref>PMID:12829604</ref> <ref>PMID:17928360</ref> <ref>PMID:22310662</ref> | + | [https://www.uniprot.org/uniprot/AGRE2_HUMAN AGRE2_HUMAN] Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment. Promotes granulocyte chemotaxis, degranulation and adhesion. In macrophages, promotes the release of inflammatory cytokines, including IL8 and TNF. Signals probably through G-proteins. Is a regulator of mast cell degranulation (PubMed:26841242).<ref>PMID:12829604</ref> <ref>PMID:17928360</ref> <ref>PMID:22310662</ref> <ref>PMID:22575658</ref> <ref>PMID:26841242</ref> |
| | == 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/bo/2bo2_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bo/2bo2_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=2bo2 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 2bo2" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Abbott, R J.M]] | + | [[Category: Large Structures]] |
| - | [[Category: Handford, P A]] | + | [[Category: Abbott RJM]] |
| - | [[Category: Knott, V]] | + | [[Category: Handford PA]] |
| - | [[Category: Lea, S M]] | + | [[Category: Knott V]] |
| - | [[Category: Mcdonnell, J M]] | + | [[Category: Lea SM]] |
| - | [[Category: Roversi, P]] | + | [[Category: McDonnell JM]] |
| - | [[Category: Spendlove, I]] | + | [[Category: Roversi P]] |
| - | [[Category: Teriete, P]] | + | [[Category: Spendlove I]] |
| - | [[Category: Calcium-binding]]
| + | [[Category: Teriete P]] |
| - | [[Category: Cd55]]
| + | |
| - | [[Category: Cd97]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: G-protein coupled receptor]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Disease
AGRE2_HUMAN Vibratory urticaria. The disease is caused by variants affecting the gene represented in this entry.
Function
AGRE2_HUMAN Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment. Promotes granulocyte chemotaxis, degranulation and adhesion. In macrophages, promotes the release of inflammatory cytokines, including IL8 and TNF. Signals probably through G-proteins. Is a regulator of mast cell degranulation (PubMed:26841242).[1] [2] [3] [4] [5]
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
CD97, the archetypal member of the EGF-TM7 protein family, is constitutively expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells following activation. The key isoform of CD97 expressed on leukocytes binds the complement regulatory protein CD55 (also termed decay-accelerating factor). CD97 has been shown recently to mediate co-stimulation of T cells via CD55. Here, we demonstrate that blocking the interaction between CD55 on monocytes and CD97 on T cells leads to inhibition of proliferation and interferon-gamma secretion. This implies that bidirectional interactions between CD97 and CD55 are involved in T cell regulation. Structural studies presented here reveal the molecular basis for this activity. We have solved the structure of EMR2, a very close homolog of CD97, using x-ray crystallography. NMR-based chemical shift mapping of the EMR2-CD55 interaction has allowed us to generate a model for the CD97-CD55 complex. The structure of the complex reveals that the T cell and complement regulatory activities of CD55 occur on opposite faces of the molecule. This suggests that CD55 might simultaneously regulate both the innate and adaptive immune responses, and we have shown that CD55 can still regulate complement when bound to CD97.
Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55.,Abbott RJ, Spendlove I, Roversi P, Fitzgibbon H, Knott V, Teriete P, McDonnell JM, Handford PA, Lea SM J Biol Chem. 2007 Jul 27;282(30):22023-32. Epub 2007 Apr 20. PMID:17449467[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH. The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood. 2003 Oct 15;102(8):2916-24. Epub 2003 Jun 26. PMID:12829604 doi:10.1182/blood-2002-11-3540
- ↑ Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RP, Lewis SM, Heinsbroek SE, Brown KA, Perretti M, Hamann J, Treacher DF, Gordon S, Stacey M. Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function. FASEB J. 2008 Mar;22(3):741-51. Epub 2007 Oct 10. PMID:17928360 doi:10.1096/fj.07-9435com
- ↑ Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP, Yona S, Stacey M, Gordon S, Chang GW, Lin HH. Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol. 2012 Apr;32(8):1408-20. doi: 10.1128/MCB.06557-11. Epub 2012 Feb, 6. PMID:22310662 doi:10.1128/MCB.06557-11
- ↑ Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X. Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett. 2012 Apr 24;586(8):1214-9. doi: 10.1016/j.febslet.2012.03.014. Epub, 2012 Mar 21. PMID:22575658 doi:http://dx.doi.org/10.1016/j.febslet.2012.03.014
- ↑ Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, Eisch AR, Long RD, Lee CC, Satorius CL, Pakstis AJ, Olivera A, Mullikin JC, Chouery E, Mégarbané A, Medlej-Hashim M, Kidd KK, Kastner DL, Metcalfe DD, Komarow HD. Vibratory Urticaria Associated with a Missense Variant in ADGRE2. N Engl J Med. 2016 Feb 18;374(7):656-63. PMID:26841242 doi:10.1056/NEJMoa1500611
- ↑ Abbott RJ, Spendlove I, Roversi P, Fitzgibbon H, Knott V, Teriete P, McDonnell JM, Handford PA, Lea SM. Structural and functional characterization of a novel T cell receptor co-regulatory protein complex, CD97-CD55. J Biol Chem. 2007 Jul 27;282(30):22023-32. Epub 2007 Apr 20. PMID:17449467 doi:M702588200
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