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{{Seed}}
[[Image:1ej5.png|left|200px]]


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==SOLUTION STRUCTURE OF THE AUTOINHIBITED CONFORMATION OF WASP==
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<StructureSection load='1ej5' size='340' side='right'caption='[[1ej5]]' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1ej5]] 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=1EJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EJ5 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1ej5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ej5 OCA], [https://pdbe.org/1ej5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ej5 RCSB], [https://www.ebi.ac.uk/pdbsum/1ej5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ej5 ProSAT]</span></td></tr>
{{STRUCTURE_1ej5| PDB=1ej5 |  SCENE= }}
</table>
== Disease ==
[https://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN] Defects in WAS are the cause of Wiskott-Aldrich syndrome (WAS) [MIM:[https://omim.org/entry/301000 301000]; also known as eczema-thrombocytopenia-immunodeficiency syndrome. WAS is an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.<ref>PMID:7753869</ref> <ref>PMID:8528198</ref> <ref>PMID:8528199</ref> <ref>PMID:8682510</ref> <ref>PMID:9126958</ref> <ref>PMID:9098856</ref> <ref>PMID:9683546</ref> <ref>PMID:9713366</ref> <ref>PMID:9445409</ref> <ref>PMID:10447259</ref> <ref>PMID:11793485</ref>  Defects in WAS are the cause of thrombocytopenia type 1 (THC1) [MIM:[https://omim.org/entry/313900 313900]. Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.<ref>PMID:8528199</ref> <ref>PMID:10447259</ref> <ref>PMID:7795648</ref> <ref>PMID:11167787</ref> <ref>PMID:11877312</ref>  Defects in WAS are a cause of neutropenia severe congenital X-linked (XLN) [MIM:[https://omim.org/entry/300299 300299]. XLN is an immunodeficiency syndrome characterized by recurrent major bacterial infections, severe congenital neutropenia, and monocytopenia.<ref>PMID:11242115</ref>
== Function ==
[https://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN] Effector protein for Rho-type GTPases. Regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria.<ref>PMID:12235133</ref> <ref>PMID:16275905</ref> <ref>PMID:18650809</ref>
== 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/ej/1ej5_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=1ej5 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Rho-family GTPase, Cdc42, can regulate the actin cytoskeleton through activation of Wiskott-Aldrich syndrome protein (WASP) family members. Activation relieves an autoinhibitory contact between the GTPase-binding domain and the carboxy-terminal region of WASP proteins. Here we report the autoinhibited structure of the GTPase-binding domain of WASP, which can be induced by the C-terminal region or by organic co-solvents. In the autoinhibited complex, intramolecular interactions with the GTPase-binding domain occlude residues of the C terminus that regulate the Arp2/3 actin-nucleating complex. Binding of Cdc42 to the GTPase-binding domain causes a dramatic conformational change, resulting in disruption of the hydrophobic core and release of the C terminus, enabling its interaction with the actin regulatory machinery. These data show that 'intrinsically unstructured' peptides such as the GTPase-binding domain of WASP can be induced into distinct structural and functional states depending on context.


===SOLUTION STRUCTURE OF THE AUTOINHIBITED CONFORMATION OF WASP===
Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.,Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK Nature. 2000 Mar 9;404(6774):151-8. PMID:10724160<ref>PMID:10724160</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1ej5" style="background-color:#fffaf0;"></div>


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==See Also==
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*[[Wiskott-Aldrich syndrome protein 3D structures|Wiskott-Aldrich syndrome protein 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 10724160 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_10724160}}
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</StructureSection>
==About this Structure==
1EJ5 is a [[Single protein]] structure of 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=1EJ5 OCA].
 
==Reference==
Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein., Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK, Nature. 2000 Mar 9;404(6774):151-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10724160 10724160]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Abdul-Manan, N.]]
[[Category: Abdul-Manan N]]
[[Category: Kakalis, L T.]]
[[Category: Kakalis LT]]
[[Category: Kim, A S.]]
[[Category: Kim AS]]
[[Category: Liu, G A.]]
[[Category: Liu GA]]
[[Category: Rosen, M K.]]
[[Category: Rosen MK]]
[[Category: Alpha helix]]
[[Category: Beta-hairpin turn]]
 
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