1l5g

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{{STRUCTURE_1l5g| PDB=1l5g | SCENE= }}
 
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===CRYSTAL STRUCTURE OF THE EXTRACELLULAR SEGMENT OF INTEGRIN AVB3 IN COMPLEX WITH AN ARG-GLY-ASP LIGAND===
 
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{{ABSTRACT_PUBMED_11884718}}
 
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==Disease==
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==CRYSTAL STRUCTURE OF THE EXTRACELLULAR SEGMENT OF INTEGRIN AVB3 IN COMPLEX WITH AN ARG-GLY-ASP LIGAND==
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[[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>
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<StructureSection load='1l5g' size='340' side='right'caption='[[1l5g]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1l5g]] is a 3 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=1L5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L5G 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">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></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=1l5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l5g OCA], [https://pdbe.org/1l5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l5g RCSB], [https://www.ebi.ac.uk/pdbsum/1l5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l5g ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. 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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== 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/l5/1l5g_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1l5g 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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The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3.
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==Function==
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Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand.,Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Arnaout MA Science. 2002 Apr 5;296(5565):151-5. Epub 2002 Mar 7. PMID:11884718<ref>PMID:11884718</ref>
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[[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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[1l5g]] is a 3 chain structure with 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=1L5G OCA].
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</div>
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<div class="pdbe-citations 1l5g" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Integrin|Integrin]]
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*[[Integrin 3D structures|Integrin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:011884718</ref><ref group="xtra">PMID:015378069</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arnaout, M A.]]
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[[Category: Large Structures]]
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[[Category: Frech, M.]]
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[[Category: Arnaout MA]]
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[[Category: Goodman, S L.]]
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[[Category: Frech M]]
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[[Category: Joachimiak, A.]]
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[[Category: Goodman SL]]
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[[Category: Stehle, T.]]
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[[Category: Joachimiak A]]
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[[Category: Xiong, J P.]]
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[[Category: Stehle T]]
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[[Category: Zhang, R.]]
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[[Category: Xiong J-P]]
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[[Category: A-domain]]
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[[Category: Zhang R]]
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[[Category: Admida]]
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[[Category: Beta-tail domain]]
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[[Category: Cage motif]]
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[[Category: Calf domain]]
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[[Category: Cell adhesion]]
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[[Category: Egf domain]]
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[[Category: Genu]]
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[[Category: Hybrid domain]]
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[[Category: Limb]]
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[[Category: Mida]]
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[[Category: Propeller]]
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[[Category: Psi domain]]
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[[Category: Rgd ligand]]
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[[Category: Thigh domain]]
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Current revision

CRYSTAL STRUCTURE OF THE EXTRACELLULAR SEGMENT OF INTEGRIN AVB3 IN COMPLEX WITH AN ARG-GLY-ASP LIGAND

PDB ID 1l5g

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