1s4x: Difference between revisions

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-[[Image:1s4x.png|left|200px]]
-{{STRUCTURE_1s4x|  PDB=1s4x  |  SCENE=  }}
+==NMR Structure of the integrin B3 cytoplasmic domain in DPC micelles==
+<StructureSection load='1s4x' size='340' side='right'caption='[[1s4x]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1s4x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S4X 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=1s4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s4x OCA], [https://pdbe.org/1s4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s4x RCSB], [https://www.ebi.ac.uk/pdbsum/1s4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s4x ProSAT]</span></td></tr>
+</table>
+== 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.
+== 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/s4/1s4x_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=1s4x ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cytoplasmic face-mediated integrin inside-out activation remains a paradigm in transmembrane signal transduction. Emerging evidence suggests that this process involves dissociation of the complex between the integrin cytoplasmic tails; however, a dynamic image of how it occurs on the membrane surface remains elusive. We show here that, whereas membrane-proximal helices of integrin alpha/beta cytoplasmic tails associate in cytoplasm-like aqueous medium, they become partially embedded into membrane-mimetic micelles when unclasped. Membrane embedding induces substantial structural changes of the cytoplasmic tails as compared to their aqueous conformations and suggests there may be an upward movement of the membrane-proximal helices into the membrane during their separation. We further demonstrate that the beta3 tail exhibits additional membrane binding site at its C terminus containing the NPLY motif. Talin, a key intracellular integrin activator, recognizes this site as well as the membrane-proximal helix, thereby promoting cytoplasmic tail separation along the membrane surface. These data provide a structural basis of membrane-mediated changes at the cytoplasmic face in regulating integrin activation and signaling.
-===NMR Structure of the integrin B3 cytoplasmic domain in DPC micelles===
+Membrane-mediated structural transitions at the cytoplasmic face during integrin activation.,Vinogradova O, Vaynberg J, Kong X, Haas TA, Plow EF, Qin J Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4094-9. Epub 2004 Mar 15. PMID:15024114<ref>PMID:15024114</ref>
-{{ABSTRACT_PUBMED_15024114}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1s4x" style="background-color:#fffaf0;"></div>
-[[1s4x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S4X OCA].
 ==See Also==
-*[[Integrin|Integrin]]
+*[[Integrin 3D structures|Integrin 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:015024114</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Haas, T A.]]
+[[Category: Large Structures]]
-[[Category: Kong, X.]]
+[[Category: Haas TA]]
-[[Category: Plow, E F.]]
+[[Category: Kong X]]
-[[Category: Qin, J.]]
+[[Category: Plow EF]]
-[[Category: Vaynberg, J.]]
+[[Category: Qin J]]
-[[Category: Vinogradova, O.]]
+[[Category: Vaynberg J]]
-[[Category: Cell adhesion]]
+[[Category: Vinogradova O]]