View source for 2rmz


==Bicelle-embedded integrin beta3 transmembrane segment==
<StructureSection load='2rmz' size='340' side='right'caption='[[2rmz]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2rmz]] 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=2RMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RMZ 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=2rmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rmz OCA], [https://pdbe.org/2rmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rmz RCSB], [https://www.ebi.ac.uk/pdbsum/2rmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rmz 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/rm/2rmz_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=2rmz ConSurf].
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== Publication Abstract from PubMed ==
Integrin adhesion receptors transduce bidirectional signals across the plasma membrane, with the integrin transmembrane domains acting as conduits in this process. Here, we report the first high-resolution structure of an integrin transmembrane domain. To assess the influence of the membrane model system, structure determinations of the beta3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-H772, is adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This relatively long transmembrane helix implies a pronounced helix tilt within a typical lipid bilayer, which facilitates the snorkeling of K716's charged side chain out of the lipid core while simultaneously immersing hydrophobic L717-I721 in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to the transfer of L717-I721 into the aqueous phase, suggesting that the reported embedding represents the preferred beta3 state. The nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the beta3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear alpha-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.

Structure of the Integrin beta3 Transmembrane Segment in Phospholipid Bicelles and Detergent Micelles.,Lau TL, Partridge AW, Ginsberg MH, Ulmer TS Biochemistry. 2008 Mar 6;. PMID:18321071<ref>PMID:18321071</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2rmz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Integrin 3D structures|Integrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ginsberg MH]]
[[Category: Lau TL]]
[[Category: Partridge AW]]
[[Category: Ulmer TS]]