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1ej5
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1cee|1CEE]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ej5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ej5 OCA], [http://www.ebi.ac.uk/pdbsum/1ej5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ej5 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Neutropenia, severe congenital, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]], Thrombocytopenia, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]], Thrombocytopenia, X-linked, intermittent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]], Wiskott-Aldrich syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300392 300392]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: beta-hairpin turn]] | [[Category: beta-hairpin turn]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:03:35 2008'' |
Revision as of 17:03, 30 March 2008
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| Related: | 1CEE
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SOLUTION STRUCTURE OF THE AUTOINHIBITED CONFORMATION OF WASP
Overview
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.
About this Structure
1EJ5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from 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:10724160
Page seeded by OCA on Sun Mar 30 20:03:35 2008
