2k42

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{{STRUCTURE_2k42| PDB=2k42 | SCENE= }}
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==Solution Structure of the GTPase Binding Domain of WASP in Complex with EspFU, an EHEC Effector==
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===Solution Structure of the GTPase Binding Domain of WASP in Complex with EspFU, an EHEC Effector===
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<StructureSection load='2k42' size='340' side='right' caption='[[2k42]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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{{ABSTRACT_PUBMED_18650809}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2k42]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_o157:h7 Escherichia coli o157:h7] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K42 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WAS, IMD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), tccP, ECs2715 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83334 Escherichia coli O157:H7])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k42 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k42 RCSB], [http://www.ebi.ac.uk/pdbsum/2k42 PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN]] Defects in WAS are the cause of Wiskott-Aldrich syndrome (WAS) [MIM:[http://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:[http://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:[http://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>
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== Function ==
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[[http://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> [[http://www.uniprot.org/uniprot/Q8X2D5_ECO57 Q8X2D5_ECO57]] Required for efficient pedestal formation in host epithelial cells during infection. Acts as an intermediate between Tir (via host BAIAP2) and host WASL/N-WASP. Directly binds and activates WASL/N-WASP, which stimulates actin polymerization and leads to the formation of actin pedestals at the sites of bacterial adhesion (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/2k42_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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During infection, enterohaemorrhagic Escherichia coli (EHEC) takes over the actin cytoskeleton of eukaryotic cells by injecting the EspF(U) protein into the host cytoplasm. EspF(U) controls actin by activating members of the Wiskott-Aldrich syndrome protein (WASP) family. Here we show that EspF(U) binds to the autoinhibitory GTPase binding domain (GBD) in WASP proteins and displaces it from the activity-bearing VCA domain (for verprolin homology, central hydrophobic and acidic regions). This interaction potently activates WASP and neural (N)-WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD-EspF(U) complex, EspF(U) forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspF(U) activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 and SH2 domains, which globally destabilize the GBD fold to release the VCA. Such diversity of mechanism in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspF(U) and Cdc42/SH2, plus high-affinity EspF(U) binding, enable EHEC to hijack the eukaryotic cytoskeletal machinery effectively.
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==Disease==
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Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U).,Cheng HC, Skehan BM, Campellone KG, Leong JM, Rosen MK Nature. 2008 Aug 21;454(7207):1009-13. Epub 2008 Jul 23. PMID:18650809<ref>PMID:18650809</ref>
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[[http://www.uniprot.org/uniprot/WASP_HUMAN WASP_HUMAN]] Defects in WAS are the cause of Wiskott-Aldrich syndrome (WAS) [MIM:[http://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:[http://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:[http://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>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://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>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[2k42]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_o157:h7 Escherichia coli o157:h7] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K42 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:018650809</ref><references group="xtra"/><references/>
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[[Category: Escherichia coli o157:h7]]
[[Category: Escherichia coli o157:h7]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 09:02, 30 September 2014

Solution Structure of the GTPase Binding Domain of WASP in Complex with EspFU, an EHEC Effector

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