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1ej5
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The Rho-family GTPase, Cdc42, can regulate the actin cytoskeleton through | + | 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== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Abdul-Manan, N.]] | [[Category: Abdul-Manan, N.]] | ||
| - | [[Category: Kakalis, L | + | [[Category: Kakalis, L T.]] |
| - | [[Category: Kim, A | + | [[Category: Kim, A S.]] |
| - | [[Category: Liu, G | + | [[Category: Liu, G A.]] |
| - | [[Category: Rosen, M | + | [[Category: Rosen, M K.]] |
[[Category: alpha helix]] | [[Category: alpha helix]] | ||
[[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 Thu Feb 21 12:28:20 2008'' |
Revision as of 10:28, 21 February 2008
|
SOLUTION STRUCTURE OF THE AUTOINHIBITED CONFORMATION OF WASP
Contents |
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.
Disease
Known diseases associated with this structure: Neutropenia, severe congenital, X-linked OMIM:[300392], Thrombocytopenia, X-linked OMIM:[300392], Thrombocytopenia, X-linked, intermittent OMIM:[300392], Wiskott-Aldrich syndrome OMIM:[300392]
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 Thu Feb 21 12:28:20 2008
