6bxb
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of an extended b3 integrin P33== | |
| + | <StructureSection load='6bxb' size='340' side='right' caption='[[6bxb]], [[Resolution|resolution]] 2.39Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6bxb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BXB 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6bxf|6bxf]], [[6bxj|6bxj]]</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=6bxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxb OCA], [http://pdbe.org/6bxb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bxb RCSB], [http://www.ebi.ac.uk/pdbsum/6bxb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Defects in ITGB3 are a cause of Glanzmann thrombasthenia (GT) [MIM:[http://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:2392682</ref> <ref>PMID:1371279</ref> <ref>PMID:1602006</ref> <ref>PMID:1438206</ref> <ref>PMID:8781422</ref> <ref>PMID:9376589</ref> <ref>PMID:9215749</ref> <ref>PMID:9790984</ref> <ref>PMID:9684783</ref> <ref>PMID:10233432</ref> <ref>PMID:11588040</ref> <ref>PMID:11897046</ref> <ref>PMID:12083483</ref> <ref>PMID:12353082</ref> <ref>PMID:15583747</ref> <ref>PMID:15634267</ref> <ref>PMID:15748237</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN]] Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 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 surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cells utilize the adhesion receptor integrins to communicate with their surroundings. Integrin activation and cellular signaling are coupled with the changes from a bent to an extended conformation. The beta3 integrins, including alphaIIbbeta3 that is essential for the function of platelets in hemostasis and thrombosis, and alphaVbeta3 that plays multiple roles in diverse cell types, have been prototypes in understanding integrin structure and function. Despite extensive structural studies, a high-resolution integrin structure in an extended conformation remains to be determined. The human beta3 Leu33Pro polymorphism, located at the PSI domain, defines the human platelet-specific alloantigen HPA-1a/b, to which immune response is a cause of post-transfusion purpura and fetal/neonatal alloimmune thrombocytopenia. The Leu33Pro substitution was also suggested to be a risk factor for thrombosis. Here we report the crystal structure of beta3 headpiece in either Leu33 or Pro33 form, both of which reveal an intermediate and a fully extended conformation coexisting in one crystal. These were used to build the high-resolution structures of full-length beta3 integrin in the intermediate and fully extended states, agreeing well with the corresponding conformations observed by electron microscopy. Our structures reveal how beta3 integrin becomes extended at its beta-knee region and how the flexibility of beta leg domains is determined. In addition, our structures reveal conformational changes of the PSI and I-EGF1 domains upon beta3 extension, which may affect the binding of conformation-dependent anti-HPA-1a alloantibodies. Our structural and functional data show that the Leu33Pro substitution doesn't directly alter the conformation and ligand binding of beta3 integrin. | ||
| - | + | Structure of an extended beta3 integrin.,Zhou D, Thinn AMM, Zhao Y, Wang Z, Zhu J Blood. 2018 Jul 17. pii: blood-2018-01-829572. doi: 10.1182/blood-2018-01-829572. PMID:30018079<ref>PMID:30018079</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 6bxb" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Zhou, D]] | [[Category: Zhou, D]] | ||
| + | [[Category: Zhu, J]] | ||
| + | [[Category: Cell adhesion]] | ||
| + | [[Category: Integrin]] | ||
Revision as of 18:44, 1 August 2018
Crystal structure of an extended b3 integrin P33
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Categories: Zhou, D | Zhu, J | Cell adhesion | Integrin
