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| - | [[Image:1dgu.jpg|left|200px]]<br /><applet load="1dgu" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1dgu" /> | |
| - | '''HOMOLOGY-BASED MODEL OF CALCIUM-SATURATED CIB (CALCIUM-AND INTEGRIN-BINDING PROTEIN)'''<br /> | |
| | | | |
| - | ==Overview== | + | ==HOMOLOGY-BASED MODEL OF CALCIUM-SATURATED CIB (CALCIUM-AND INTEGRIN-BINDING PROTEIN)== |
| - | Calcium- and integrin-binding protein (CIB) binds to the 20-residue, alphaIIb cytoplasmic domain of platelet alphaIIbbeta3 integrin. Amino acid, sequence similarities with calmodulin (CaM) and calcineurin B (CnB), allowed the construction of homology-based models of calcium-saturated CIB, as well as apo-CIB. In addition, the solution structure of the alphaIIb, cytoplasmic domain in 45% aqueous trifluoroethanol was solved by, conventional two-dimensional NMR methods. The models indicate that the, N-terminal domain of CIB possesses a number of positively charged residues, in its binding site that could interact with the acidic carboxy-terminal, LEEDDEEGE sequence of alphaIIb. The C-terminal domain of CIB seems, well-suited to bind the sequence WKVGFFKR, which forms a well-structured, alpha helix; this is analogous to calmodulin and calcineurin B, which also, bind alpha helices. Similarities between the C-terminal domains of CIB and, calmodulin suggest that binding of CIB to the cytoplasmic domain of, alphaIIb may be affected by fluctuations in the intracellular calcium, concentration. | + | <StructureSection load='1dgu' size='340' side='right'caption='[[1dgu]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1dgu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DGU FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1dgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dgu OCA], [https://pdbe.org/1dgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dgu RCSB], [https://www.ebi.ac.uk/pdbsum/1dgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dgu ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [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> |
| | + | == 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/dg/1dgu_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1dgu ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Calcium- and integrin-binding protein (CIB) binds to the 20-residue alphaIIb cytoplasmic domain of platelet alphaIIbbeta3 integrin. Amino acid sequence similarities with calmodulin (CaM) and calcineurin B (CnB) allowed the construction of homology-based models of calcium-saturated CIB as well as apo-CIB. In addition, the solution structure of the alphaIIb cytoplasmic domain in 45% aqueous trifluoroethanol was solved by conventional two-dimensional NMR methods. The models indicate that the N-terminal domain of CIB possesses a number of positively charged residues in its binding site that could interact with the acidic carboxy-terminal LEEDDEEGE sequence of alphaIIb. The C-terminal domain of CIB seems well-suited to bind the sequence WKVGFFKR, which forms a well-structured alpha helix; this is analogous to calmodulin and calcineurin B, which also bind alpha helices. Similarities between the C-terminal domains of CIB and calmodulin suggest that binding of CIB to the cytoplasmic domain of alphaIIb may be affected by fluctuations in the intracellular calcium concentration. |
| | | | |
| - | ==Disease==
| + | Structures of the platelet calcium- and integrin-binding protein and the alphaIIb-integrin cytoplasmic domain suggest a mechanism for calcium-regulated recognition; homology modelling and NMR studies.,Hwang PM, Vogel HJ J Mol Recognit. 2000 Mar-Apr;13(2):83-92. PMID:10822252<ref>PMID:10822252</ref> |
| - | Known disease associated with this structure: Multiple endocrine neoplasia, type IV OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600778 600778]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1DGU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of 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=1DGU OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 1dgu" style="background-color:#fffaf0;"></div> |
| - | ==Reference== | + | == References == |
| - | Structures of the platelet calcium- and integrin-binding protein and the alphaIIb-integrin cytoplasmic domain suggest a mechanism for calcium-regulated recognition; homology modelling and NMR studies., Hwang PM, Vogel HJ, J Mol Recognit. 2000 Mar-Apr;13(2):83-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10822252 10822252]
| + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Hwang, P.M.]] | + | [[Category: Hwang PM]] |
| - | [[Category: Vogel, H.J.]] | + | [[Category: Vogel HJ]] |
| - | [[Category: blood clotting]]
| + | |
| - | [[Category: ef-hands]]
| + | |
| - | [[Category: helical]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:39:49 2008''
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4] [5] [6]
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
Calcium- and integrin-binding protein (CIB) binds to the 20-residue alphaIIb cytoplasmic domain of platelet alphaIIbbeta3 integrin. Amino acid sequence similarities with calmodulin (CaM) and calcineurin B (CnB) allowed the construction of homology-based models of calcium-saturated CIB as well as apo-CIB. In addition, the solution structure of the alphaIIb cytoplasmic domain in 45% aqueous trifluoroethanol was solved by conventional two-dimensional NMR methods. The models indicate that the N-terminal domain of CIB possesses a number of positively charged residues in its binding site that could interact with the acidic carboxy-terminal LEEDDEEGE sequence of alphaIIb. The C-terminal domain of CIB seems well-suited to bind the sequence WKVGFFKR, which forms a well-structured alpha helix; this is analogous to calmodulin and calcineurin B, which also bind alpha helices. Similarities between the C-terminal domains of CIB and calmodulin suggest that binding of CIB to the cytoplasmic domain of alphaIIb may be affected by fluctuations in the intracellular calcium concentration.
Structures of the platelet calcium- and integrin-binding protein and the alphaIIb-integrin cytoplasmic domain suggest a mechanism for calcium-regulated recognition; homology modelling and NMR studies.,Hwang PM, Vogel HJ J Mol Recognit. 2000 Mar-Apr;13(2):83-92. PMID:10822252[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Naik UP, Naik MU. Association of CIB with GPIIb/IIIa during outside-in signaling is required for platelet spreading on fibrinogen. Blood. 2003 Aug 15;102(4):1355-62. Epub 2003 Apr 24. PMID:12714504 doi:10.1182/blood-2003-02-0591
- ↑ Naik MU, Naik UP. Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Blood. 2003 Nov 15;102(10):3629-36. Epub 2003 Jul 24. PMID:12881299 doi:10.1182/blood-2003-05-1703
- ↑ Tahara E Jr, Tahara H, Kanno M, Naka K, Takeda Y, Matsuzaki T, Yamazaki R, Ishihara H, Yasui W, Barrett JC, Ide T, Tahara E. G1P3, an interferon inducible gene 6-16, is expressed in gastric cancers and inhibits mitochondrial-mediated apoptosis in gastric cancer cell line TMK-1 cell. Cancer Immunol Immunother. 2005 Aug;54(8):729-40. Epub 2005 Feb 1. PMID:15685448 doi:10.1007/s00262-004-0645-2
- ↑ Hennigs JK, Burhenne N, Stahler F, Winnig M, Walter B, Meyerhof W, Schmale H. Sweet taste receptor interacting protein CIB1 is a general inhibitor of InsP3-dependent Ca2+ release in vivo. J Neurochem. 2008 Sep;106(5):2249-62. doi: 10.1111/j.1471-4159.2008.05563.x. PMID:18627437 doi:10.1111/j.1471-4159.2008.05563.x
- ↑ Yoon KW, Cho JH, Lee JK, Kang YH, Chae JS, Kim YM, Kim J, Kim EK, Kim SE, Baik JH, Naik UP, Cho SG, Choi EJ. CIB1 functions as a Ca(2+)-sensitive modulator of stress-induced signaling by targeting ASK1. Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17389-94. doi:, 10.1073/pnas.0812259106. Epub 2009 Sep 29. PMID:19805025 doi:10.1073/pnas.0812259106
- ↑ Kostyak JC, Naik UP. Calcium- and integrin-binding protein 1 regulates endomitosis and its interaction with Polo-like kinase 3 is enhanced in endomitotic Dami cells. PLoS One. 2011 Jan 14;6(1):e14513. doi: 10.1371/journal.pone.0014513. PMID:21264284 doi:10.1371/journal.pone.0014513
- ↑ Hwang PM, Vogel HJ. Structures of the platelet calcium- and integrin-binding protein and the alphaIIb-integrin cytoplasmic domain suggest a mechanism for calcium-regulated recognition; homology modelling and NMR studies. J Mol Recognit. 2000 Mar-Apr;13(2):83-92. PMID:10822252 doi:<83::AID-JMR491>3.0.CO;2-A http://dx.doi.org/10.1002/(SICI)1099-1352(200003/04)13:2<83::AID-JMR491>3.0.CO;2-A
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