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| - | [[Image:2uv3.gif|left|200px]]<br /><applet load="2uv3" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2uv3, resolution 1.8Å" /> | |
| - | '''STRUCTURE OF THE SIGNAL-REGULATORY PROTEIN (SIRP) ALPHA DOMAIN THAT BINDS CD47.'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Structure of the signal-regulatory protein (SIRP) alpha domain that binds CD47.== |
| - | Signal regulatory protein (SIRP) alpha is a membrane receptor that sends, inhibitory signals to myeloid cells by engagement of CD47. The high, resolution x-ray structure of the N-terminal ligand binding domain shows, it to have a distinctive immunoglobulin superfamily V-like fold., Site-directed mutagenesis suggests that CD47 is bound at a surface, involving the BC, FG, and DE loops, which distinguishes it from other, immunoglobulin superfamily surface proteins that use the faces of the, fold, but resembles antigen receptors. The SIRP interaction is confined to, a single domain, and its use of an extended DE loop strengthens the, similarity with T cell receptor binding and the suggestion that they are, closely related in evolution. The employment of loops to form the, CD47-binding surface provides a mechanism for small sequence changes to, modulate binding specificity, explaining the different binding properties, of SIRP family members. | + | <StructureSection load='2uv3' size='340' side='right'caption='[[2uv3]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2uv3]] 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=2UV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UV3 FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2uv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uv3 OCA], [https://pdbe.org/2uv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uv3 RCSB], [https://www.ebi.ac.uk/pdbsum/2uv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uv3 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SHPS1_HUMAN SHPS1_HUMAN] Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.<ref>PMID:10469599</ref> <ref>PMID:11509594</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uv/2uv3_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </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/main_output.php?pdb_ID=2uv3 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Signal regulatory protein (SIRP) alpha is a membrane receptor that sends inhibitory signals to myeloid cells by engagement of CD47. The high resolution x-ray structure of the N-terminal ligand binding domain shows it to have a distinctive immunoglobulin superfamily V-like fold. Site-directed mutagenesis suggests that CD47 is bound at a surface involving the BC, FG, and DE loops, which distinguishes it from other immunoglobulin superfamily surface proteins that use the faces of the fold, but resembles antigen receptors. The SIRP interaction is confined to a single domain, and its use of an extended DE loop strengthens the similarity with T cell receptor binding and the suggestion that they are closely related in evolution. The employment of loops to form the CD47-binding surface provides a mechanism for small sequence changes to modulate binding specificity, explaining the different binding properties of SIRP family members. |
| | | | |
| - | ==About this Structure==
| + | The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors.,Hatherley D, Harlos K, Dunlop DC, Stuart DI, Barclay AN J Biol Chem. 2007 May 11;282(19):14567-75. Epub 2007 Mar 16. PMID:17369261<ref>PMID:17369261</ref> |
| - | 2UV3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Mes+Binding+Site+For+Chain+B'>AC1</scene>, <scene name='pdbsite=AC2:Mes+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Chain+B'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Chain+A'>AC7</scene> and <scene name='pdbsite=AC8:So4+Binding+Site+For+Chain+A'>AC8</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UV3 OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors., Hatherley D, Harlos K, Dunlop DC, Stuart DI, Barclay AN, J Biol Chem. 2007 May 11;282(19):14567-75. Epub 2007 Mar 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17369261 17369261]
| + | </div> |
| | + | <div class="pdbe-citations 2uv3" style="background-color:#fffaf0;"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Barclay, A.N.]] | + | [[Category: Barclay AN]] |
| - | [[Category: Dunlop, D.C.]] | + | [[Category: Dunlop DC]] |
| - | [[Category: Harlos, K.]] | + | [[Category: Harlos K]] |
| - | [[Category: Hatherley, D.]] | + | [[Category: Hatherley D]] |
| - | [[Category: Stuart, D.I.]] | + | [[Category: Stuart DI]] |
| - | [[Category: MES]]
| + | |
| - | [[Category: SO4]]
| + | |
| - | [[Category: alternative splicing]]
| + | |
| - | [[Category: cd47-binding domain of sirp-alpha]]
| + | |
| - | [[Category: glycoprotein]]
| + | |
| - | [[Category: human sirp-alpha n terminal v domain]]
| + | |
| - | [[Category: immunoglobulin domain]]
| + | |
| - | [[Category: membrane]]
| + | |
| - | [[Category: phosphorylation]]
| + | |
| - | [[Category: polymorphism]]
| + | |
| - | [[Category: receptor]]
| + | |
| - | [[Category: sh3-binding]]
| + | |
| - | [[Category: signal-regulatory protein alpha]]
| + | |
| - | [[Category: transmembrane]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:47:15 2008''
| + | |
| Structural highlights
Function
SHPS1_HUMAN Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.[1] [2]
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
Signal regulatory protein (SIRP) alpha is a membrane receptor that sends inhibitory signals to myeloid cells by engagement of CD47. The high resolution x-ray structure of the N-terminal ligand binding domain shows it to have a distinctive immunoglobulin superfamily V-like fold. Site-directed mutagenesis suggests that CD47 is bound at a surface involving the BC, FG, and DE loops, which distinguishes it from other immunoglobulin superfamily surface proteins that use the faces of the fold, but resembles antigen receptors. The SIRP interaction is confined to a single domain, and its use of an extended DE loop strengthens the similarity with T cell receptor binding and the suggestion that they are closely related in evolution. The employment of loops to form the CD47-binding surface provides a mechanism for small sequence changes to modulate binding specificity, explaining the different binding properties of SIRP family members.
The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors.,Hatherley D, Harlos K, Dunlop DC, Stuart DI, Barclay AN J Biol Chem. 2007 May 11;282(19):14567-75. Epub 2007 Mar 16. PMID:17369261[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Timms JF, Swanson KD, Marie-Cardine A, Raab M, Rudd CE, Schraven B, Neel BG. SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages. Curr Biol. 1999 Aug 26;9(16):927-30. PMID:10469599
- ↑ Latour S, Tanaka H, Demeure C, Mateo V, Rubio M, Brown EJ, Maliszewski C, Lindberg FP, Oldenborg A, Ullrich A, Delespesse G, Sarfati M. Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation. J Immunol. 2001 Sep 1;167(5):2547-54. PMID:11509594
- ↑ Hatherley D, Harlos K, Dunlop DC, Stuart DI, Barclay AN. The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors. J Biol Chem. 2007 May 11;282(19):14567-75. Epub 2007 Mar 16. PMID:17369261 doi:10.1074/jbc.M611511200
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