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2k9j

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[[Image:2k9j.png|left|200px]]
 
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==Integrin alphaIIb-beta3 transmembrane complex==
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The line below this paragraph, containing "STRUCTURE_2k9j", creates the "Structure Box" on the page.
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<StructureSection load='2k9j' size='340' side='right'caption='[[2k9j]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2k9j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Integrin'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_2 10.2210/rcsb_pdb/mom_2011_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K9J 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=2k9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k9j OCA], [https://pdbe.org/2k9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k9j RCSB], [https://www.ebi.ac.uk/pdbsum/2k9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k9j ProSAT]</span></td></tr>
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{{STRUCTURE_2k9j| PDB=2k9j | 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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== 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/k9/2k9j_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=2k9j ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Heterodimeric integrin adhesion receptors regulate cell migration, survival and differentiation in metazoa by communicating signals bi-directionally across the plasma membrane. Protein engineering and mutagenesis studies have suggested that the dissociation of a complex formed by the single-pass transmembrane (TM) segments of the alpha and beta subunits is central to these signalling events. Here, we report the structure of the integrin alphaIIbbeta3 TM complex, structure-based site-directed mutagenesis and lipid embedding estimates to reveal the structural event that underlies the transition from associated to dissociated states, that is, TM signalling. The complex is stabilized by glycine-packing mediated TM helix crossing within the extracellular membrane leaflet, and by unique hydrophobic and electrostatic bridges in the intracellular leaflet that mediate an unusual, asymmetric association of the 24- and 29-residue alphaIIb and beta3 TM helices. The structurally unique, highly conserved integrin alphaIIbbeta3 TM complex rationalizes bi-directional signalling and represents the first structure of a heterodimeric TM receptor complex.
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===Integrin alphaIIb-beta3 transmembrane complex===
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The structure of the integrin alphaIIbbeta3 transmembrane complex explains integrin transmembrane signalling.,Lau TL, Kim C, Ginsberg MH, Ulmer TS EMBO J. 2009 May 6;28(9):1351-61. Epub 2009 Mar 12. PMID:19279667<ref>PMID:19279667</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>
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<div class="pdbe-citations 2k9j" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19279667}}, adds the Publication Abstract to the page
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*[[Integrin 3D structures|Integrin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19279667 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19279667}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[2k9j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2011 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Integrin'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2011_2 10.2210/rcsb_pdb/mom_2011_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K9J OCA].
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==Reference==
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<ref group="xtra">PMID:19279667</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Integrin]]
[[Category: Integrin]]
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[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Ginsberg, M H.]]
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[[Category: Ginsberg MH]]
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[[Category: Kim, C.]]
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[[Category: Kim C]]
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[[Category: Lau, T.]]
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[[Category: Lau T]]
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[[Category: Ulmer, T S.]]
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[[Category: Ulmer TS]]

Current revision

Integrin alphaIIb-beta3 transmembrane complex

PDB ID 2k9j

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