1dpq

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{{Seed}}
 
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[[Image:1dpq.png|left|200px]]
 
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==SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.==
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The line below this paragraph, containing "STRUCTURE_1dpq", creates the "Structure Box" on the page.
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<StructureSection load='1dpq' size='340' side='right'caption='[[1dpq]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1dpq]] 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=1DPQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DPQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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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=1dpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dpq OCA], [https://pdbe.org/1dpq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dpq RCSB], [https://www.ebi.ac.uk/pdbsum/1dpq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dpq ProSAT]</span></td></tr>
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{{STRUCTURE_1dpq| PDB=1dpq | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN] Defects in ITGA2B are a cause of Glanzmann thrombasthenia (GT) [MIM:[https://omim.org/entry/273800 273800]; also known as thrombasthenia of Glanzmann and Naegeli. GT is the most common inherited disease of platelets. It is an autosomal recessive disorder characterized by mucocutaneous bleeding of mild-to-moderate severity and the inability of this integrin to recognize macromolecular or synthetic peptide ligands. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb/beta-3 complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the glycoprotein IIb/beta-3 complex at reduced levels (5-20% controls), have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The platelets of GT 'variants' have normal or near normal (60-100%) expression of dysfunctional receptors.<ref>PMID:8282784</ref> <ref>PMID:7508443</ref> <ref>PMID:7706461</ref> <ref>PMID:8704171</ref> <ref>PMID:9215749</ref> <ref>PMID:9473221</ref> <ref>PMID:9763559</ref> <ref>PMID:9722314</ref> <ref>PMID:9734640</ref> <ref>PMID:9920835</ref> <ref>PMID:10607701</ref> <ref>PMID:11798398</ref> <ref>PMID:12181054</ref> <ref>PMID:12083483</ref> <ref>PMID:12424194</ref> <ref>PMID:12506038</ref> <ref>PMID:15099289</ref> <ref>PMID:15219201</ref> <ref>PMID:17018384</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN] Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A key step in the activation of heterodimeric integrin adhesion receptors is the transmission of an agonist-induced cellular signal from the short alpha- and/or beta-cytoplasmic tails to the extracellular domains of the receptor. The structural details of how the cytoplasmic tails mediate such an inside-out signaling process remain unclear. We report herein the NMR structures of a membrane-anchored cytoplasmic tail of the alpha(IIb)-subunit and of a mutant alpha(IIb)-cytoplasmic tail that renders platelet integrin alpha(IIb)beta(3) constitutively active. The structure of the wild-type alpha(IIb)-cytoplasmic tail reveals a "closed" conformation where the highly conserved N-terminal membrane-proximal region forms an alpha-helix followed by a turn, and the acidic C-terminal loop interacts with the N-terminal helix. The structure of the active mutant is significantly different, having an "open" conformation where the interactions between the N-terminal helix and C-terminal region are abolished. Consistent with these structural differences, the two peptides differ in function: the wild-type peptide suppressed alpha(IIb)beta(3) activation, whereas the mutant peptide did not. These results provide an atomic explanation for extensive biochemical/mutational data and support a conformation-based "on/off switch" model for integrin activation.
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===SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.===
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A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit.,Vinogradova O, Haas T, Plow EF, Qin J Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:10677482<ref>PMID:10677482</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1dpq" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 10677482 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_10677482}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Homo sapiens]]
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1DPQ is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DPQ OCA].
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[[Category: Large Structures]]
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[[Category: Haas T]]
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==Reference==
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[[Category: Plow EF]]
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A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit., Vinogradova O, Haas T, Plow EF, Qin J, Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10677482 10677482]
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[[Category: Qin J]]
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[[Category: Single protein]]
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[[Category: Vinogradova O]]
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[[Category: Haas, T.]]
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[[Category: Plow, E F.]]
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[[Category: Qin, J.]]
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[[Category: Vinogradova, O.]]
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[[Category: Helix]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:25:59 2008''
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Current revision

SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.

PDB ID 1dpq

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