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Sci. STKE, 14 March 2000
Vol. 2000, Issue 23, p. tw10
[DOI: 10.1126/stke.2000.23.tw10]


Structural Biology Binding Partners Dictate WASP Conformation

Actin polymerization can be regulated by the Rho family GTPases (such as CDC42) through a signaling pathway that involves the activation of Wiskott-Aldrich syndrome protein (WASP) family members and the actin-nucleating complex Arp2/3. The GTPase-binding domain (GBD) of WASP binds to CDC42 but also binds to a region at its own COOH-terminus called the VCA region. A structural comparison of GBD in complex with CDC42 or the VCA region reveals that GBD assumes quite different conformations depending on its binding partner. Kim et al. report that when bound to VCA, an autoinhibitory fold is created in the WASP GBD that sequesters its Arp2/3-binding domain. In contrast, when bound to CDC42, the autoinhibitory fold is disrupted and releases the Arp2/3-interacting region. Hence, the structural data confirm the idea that GBD is somewhat plastic and that a conformational change is needed to release WASP autoinhibition.

Kim, A.S., Kakalis, L.T., Abdul-Manan, N., Liu, G.A., and Rosen, M.K. (2000) Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein. Nature 404: 151-158. [Online Journal]

Citation: Binding Partners Dictate WASP Conformation. Sci. STKE 2000, tw10 (2000).

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