1dpq

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_1dpq| PDB=1dpq | SCENE= }}
+
==SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.==
-
===SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.===
+
<StructureSection load='1dpq' size='340' side='right' caption='[[1dpq]], [[NMR_Ensembles_of_Models | 11 NMR models]]' scene=''>
-
{{ABSTRACT_PUBMED_10677482}}
+
== Structural highlights ==
-
 
+
<table><tr><td colspan='2'>[[1dpq]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DPQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DPQ FirstGlance]. <br>
-
==Disease==
+
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dpk|1dpk]]</td></tr>
-
[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B 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: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>
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dpq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dpq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dpq RCSB], [http://www.ebi.ac.uk/pdbsum/1dpq PDBsum]</span></td></tr>
-
 
+
</table>
-
==Function==
+
== Disease ==
 +
[[http://www.uniprot.org/uniprot/ITA2B_HUMAN ITA2B_HUMAN]] Defects in ITGA2B 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: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 ==
[[http://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.
[[http://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.
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
A key step in the activation of heterodimeric integrin adhesion receptors is the transmission of an agonist-induced cellular signal from the short alpha- and/or beta-cytoplasmic tails to the extracellular domains of the receptor. The structural details of how the cytoplasmic tails mediate such an inside-out signaling process remain unclear. We report herein the NMR structures of a membrane-anchored cytoplasmic tail of the alpha(IIb)-subunit and of a mutant alpha(IIb)-cytoplasmic tail that renders platelet integrin alpha(IIb)beta(3) constitutively active. The structure of the wild-type alpha(IIb)-cytoplasmic tail reveals a "closed" conformation where the highly conserved N-terminal membrane-proximal region forms an alpha-helix followed by a turn, and the acidic C-terminal loop interacts with the N-terminal helix. The structure of the active mutant is significantly different, having an "open" conformation where the interactions between the N-terminal helix and C-terminal region are abolished. Consistent with these structural differences, the two peptides differ in function: the wild-type peptide suppressed alpha(IIb)beta(3) activation, whereas the mutant peptide did not. These results provide an atomic explanation for extensive biochemical/mutational data and support a conformation-based "on/off switch" model for integrin activation.
-
==About this Structure==
+
A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit.,Vinogradova O, Haas T, Plow EF, Qin J Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:10677482<ref>PMID:10677482</ref>
-
[[1dpq]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DPQ OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
<ref group="xtra">PMID:010677482</ref><references group="xtra"/><references/>
+
</div>
-
[[Category: Haas, T.]]
+
== References ==
-
[[Category: Plow, E F.]]
+
<references/>
-
[[Category: Qin, J.]]
+
__TOC__
-
[[Category: Vinogradova, O.]]
+
</StructureSection>
 +
[[Category: Haas, T]]
 +
[[Category: Plow, E F]]
 +
[[Category: Qin, J]]
 +
[[Category: Vinogradova, O]]
[[Category: Cell adhesion]]
[[Category: Cell adhesion]]
[[Category: Helix]]
[[Category: Helix]]

Revision as of 12:19, 18 December 2014

SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1dpq"
Personal tools