1m8o: Difference between revisions

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-[[Image:1m8o.jpg|left|200px]]<br /><applet load="1m8o" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1m8o" />
-'''Platelet integrin alfaIIb-beta3 cytoplasmic domain'''<br />
-==Overview==
+==Platelet integrin alfaIIb-beta3 cytoplasmic domain==
-Activation of the ligand binding function of integrin heterodimers, requires transmission of an "inside-out" signal from their small, intracellular segments to their large extracellular domains. The structure, of the cytoplasmic domain of a prototypic integrin alpha(IIb)beta(3) has, been solved by NMR and reveals multiple hydrophobic and electrostatic, contacts within the membrane-proximal helices of its alpha and the beta, cytoplasmic tails. The interface interactions are disrupted by point, mutations or the cytoskeletal protein talin that are known to activate the, receptor. These results provide a structural mechanism by which a, handshake between the alpha and the beta cytoplasmic tails restrains the, integrin in a resting state and unclasping of this interaction triggers, the inside-out conformational signal that leads to receptor activation.
+<StructureSection load='1m8o' size='340' side='right'caption='[[1m8o]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1m8o]] 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=1M8O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M8O FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1m8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m8o OCA], [https://pdbe.org/1m8o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m8o RCSB], [https://www.ebi.ac.uk/pdbsum/1m8o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m8o ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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>
+== Function ==
+[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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m8/1m8o_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1m8o ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Activation of the ligand binding function of integrin heterodimers requires transmission of an "inside-out" signal from their small intracellular segments to their large extracellular domains. The structure of the cytoplasmic domain of a prototypic integrin alpha(IIb)beta(3) has been solved by NMR and reveals multiple hydrophobic and electrostatic contacts within the membrane-proximal helices of its alpha and the beta cytoplasmic tails. The interface interactions are disrupted by point mutations or the cytoskeletal protein talin that are known to activate the receptor. These results provide a structural mechanism by which a handshake between the alpha and the beta cytoplasmic tails restrains the integrin in a resting state and unclasping of this interaction triggers the inside-out conformational signal that leads to receptor activation.
-==Disease==
+A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face.,Vinogradova O, Velyvis A, Velyviene A, Hu B, Haas T, Plow E, Qin J Cell. 2002 Sep 6;110(5):587-97. PMID:12230976<ref>PMID:12230976</ref>
-Known diseases associated with this structure: Glanzmann thrombasthenia, type A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607759 607759]], Glanzmann thrombasthenia, type B OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173470 173470]], Thrombocytopenia, neonatal alloimmune OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607759 607759]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-M8O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1M8O OCA].
+</div>
+<div class="pdbe-citations 1m8o" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face., Vinogradova O, Velyvis A, Velyviene A, Hu B, Haas T, Plow E, Qin J, Cell. 2002 Sep 6;110(5):587-97. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12230976 12230976]
+*[[Integrin 3D structures|Integrin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Integrin]]
-[[Category: Haas, T.]]
+[[Category: Large Structures]]
-[[Category: Hu, B.]]
+[[Category: RCSB PDB Molecule of the Month]]
-[[Category: Plow, E.F.]]
+[[Category: Haas T]]
-[[Category: Qin, J.]]
+[[Category: Hu B]]
-[[Category: Velyviene, A.]]
+[[Category: Plow EF]]
-[[Category: Velyvis, A.]]
+[[Category: Qin J]]
-[[Category: Vinogradova, O.]]
+[[Category: Velyviene A]]
-[[Category: alfa helix]]
+[[Category: Velyvis A]]
-[[Category: platelet]]
+[[Category: Vinogradova O]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:22:43 2008''