1y1a

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[[Image:1y1a.gif|left|200px]]<br /><applet load="1y1a" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1y1a, resolution 2.30&Aring;" />
 
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'''CRYSTAL STRUCTURE OF CALCIUM AND INTEGRIN BINDING PROTEIN'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF CALCIUM AND INTEGRIN BINDING PROTEIN==
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Calcium- and integrin-binding protein 1 (CIB1) is involved in the process of platelet aggregation by binding the cytoplasmic tail of the alpha(IIb) subunit of the platelet-specific integrin alpha(Iib)beta(3). Although poorly understood, it is widely believed that CIB1 acts as a global signaling regulator because it is expressed in many tissues that do not express integrin alpha(Iib)beta(3). We report the structure of human CIB1 to a resolution of 2.3 A, crystallized as a dimer. The dimer interface includes an extensive hydrophobic patch in a crystal form with 80% solvent content. Although the dimer form of CIB1 may not be physiologically relevant, this intersub-unit surface is likely to be linked to alpha(IIb) binding and to the binding of other signaling partner proteins. The C-terminal domain of CIB1 is structurally similar to other EF-hand proteins such as calmodulin and calcineurin B. Despite structural homology to the C-terminal domain, the N-terminal domain of CIB1 lacks calcium-binding sites. The structure of CIB1 revealed a complex with a molecule of glutathione in the reduced state bond to the N-terminal domain of one of the two subunits poised to interact with the free thiol of C35. Glutathione bound in this fashion suggests CIB1 may be redox regulated. Next to the bound GSH, the orientation of residues C35, H31, and S48 is suggestive of a cysteine-type protein phosphatase active site. The potential enzymatic activity of CIB1 is discussed and suggests a mechanism by which it regulates a wide variety of proteins in cells in addition to platelets.
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<StructureSection load='1y1a' size='340' side='right'caption='[[1y1a]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1y1a]] 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=1Y1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y1A FirstGlance]. <br>
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Known disease associated with this structure: Multiple endocrine neoplasia, type IV OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600778 600778]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<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=GSH:GLUTATHIONE'>GSH</scene></td></tr>
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==About this Structure==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1y1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y1a OCA], [https://pdbe.org/1y1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y1a RCSB], [https://www.ebi.ac.uk/pdbsum/1y1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y1a ProSAT]</span></td></tr>
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1Y1A 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=CA:'>CA</scene> and <scene name='pdbligand=GSH:'>GSH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=CA1:Ca+Binding+Site+1,+Ef-Hand,+Chain+A'>CA1</scene>, <scene name='pdbsite=CA2:Ca+Binding+Site+2,+Ef-Hand,+Chain+A'>CA2</scene>, <scene name='pdbsite=CA3:Ca+Binding+Site+3,+Ef-Hand,+Chain+B'>CA3</scene> and <scene name='pdbsite=CA4:Ca+Binding+Site+4,+Ef-Hand,+Chain+B'>CA4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y1A OCA].
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</table>
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== Function ==
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==Reference==
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[https://www.uniprot.org/uniprot/CIB1_HUMAN CIB1_HUMAN] May convert the inactive conformation of integrin alpha-IIb/beta3 to an active form through binding to the integrin cytoplasmic domain. Induces cell migration and spreading mediated through integrin (possibly via focal adhesion complexes). Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. May play a role in regulation of apoptosis. Interacts with and up-regulates PTK2/FAK1 activity. Down regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Participates in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation.<ref>PMID:12714504</ref> <ref>PMID:12881299</ref> <ref>PMID:15685448</ref> <ref>PMID:18627437</ref> <ref>PMID:19805025</ref> <ref>PMID:21264284</ref>
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The crystal structure of calcium- and integrin-binding protein 1: insights into redox regulated functions., Blamey CJ, Ceccarelli C, Naik UP, Bahnson BJ, Protein Sci. 2005 May;14(5):1214-21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15840829 15840829]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y1/1y1a_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1y1a ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bahnson, B J.]]
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[[Category: Bahnson BJ]]
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[[Category: Blamey, C J.]]
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[[Category: Blamey CJ]]
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[[Category: Ceccarelli, C.]]
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[[Category: Ceccarelli C]]
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[[Category: Naik, U P.]]
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[[Category: Naik UP]]
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[[Category: CA]]
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[[Category: GSH]]
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[[Category: calcium]]
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[[Category: calcium-binding protein]]
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[[Category: ef-hand]]
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[[Category: glutathiolation]]
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[[Category: glutathione]]
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[[Category: integrin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:48 2008''
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Current revision

CRYSTAL STRUCTURE OF CALCIUM AND INTEGRIN BINDING PROTEIN

PDB ID 1y1a

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