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1ej5

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Revision as of 17:03, 30 March 2008 by OCA (Talk | contribs)
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PDB ID 1ej5

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Related: 1CEE


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

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