View source for 4cak


==Three-dimensional reconstruction of intact human integrin alphaIIbbeta3 in a phospholipid bilayer nanodisc==
<SX load='4cak' size='340' side='right' viewer='molstar' caption='[[4cak]], [[Resolution|resolution]] 20.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cak]] 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=4CAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CAK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 20.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4cak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cak OCA], [https://pdbe.org/4cak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cak RCSB], [https://www.ebi.ac.uk/pdbsum/4cak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cak ProSAT]</span></td></tr>
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== Disease ==
[https://www.uniprot.org/uniprot/ITB3_HUMAN ITB3_HUMAN] Defects in ITGB3 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: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 ==
[https://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.
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== Publication Abstract from PubMed ==
Integrin alphaIIbbeta3 plays a central role in hemostasis and thrombosis. We provide the first three-dimensional reconstruction of intact purified alphaIIbbeta3 in a nanodisc lipid bilayer. Unlike previous models, it shows that the ligand binding head domain is on top, pointing away from the membrane. Moreover, unlike the crystal structure of the recombinant ectodomain, the lower legs are not parallel, straight and adjacent. Rather the alphaIIb lower leg is bent between the calf-1 and calf-2 domains and the beta3 I-EGF 2-4 domains are freely coiled rather than in a cleft between the beta3 headpiece and the alphaIIb lower leg. Our data indicate an important role for the region that links the distal calf-2 and beta-tail domains to their respective TM domains in transmitting the conformational changes in the TM domains associated with inside-out activation.

Three-dimensional reconstruction of intact human integrin alphaIIbbeta3; new implications for activation-dependent ligand binding.,Choi WS, Rice WJ, Stokes DL, Coller BS Blood. 2013 Oct 17. PMID:24136164<ref>PMID:24136164</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4cak" style="background-color:#fffaf0;"></div>

==See Also==
*[[Integrin 3D structures|Integrin 3D structures]]
== References ==
<references/>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Choi WS]]
[[Category: Coller BS]]
[[Category: Rice WJ]]
[[Category: Stokes DL]]