We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.
- Authors
Kim, A S; Kakalis, L T; Abdul-Manan, N; Liu, G A; Rosen, M K
- Abstract
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.
- Publication
Nature, 2000, Vol 404, Issue 6774, p151
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/35004513