1ej5
From Proteopedia
|
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 Fri Feb 15 15:43:38 2008
