Bunney, Tom D, Opaleye, Olanivi, Roe, S Mark, Vatter, Petra, Baxendale, Rhona W, Walliser, Claudia, Everett, Katy L, Josephs, Michelle B, Christow, Carolin, Rodrigues-Lima, Fernando, Gierschik, Peter, Pearl, Laurence H and Katan, Matilda (2009) Structural Insights into Formation of an Active Signaling Complex between Rac and Phospholipase C Gamma 2. Molecular Cell, 34 (2). pp. 223-233. ISSN 1097-2765

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Abstract

Rho family GTPases are important cellular switches and control a number of physiological functions. Understanding the molecular basis of interaction of these GTPases with their effectors is crucial in understanding their functions in the cell. Here we present the crystal structure of the complex of Rac2 bound to the split pleckstrin homology (spPH) domain of phospholipase C-gamma(2) (PLC gamma(2)). Based on this structure, we illustrate distinct requirements for PLC gamma(2) activation by Rac and EGF and generate Rac effector mutants that specifically block activation of PLC gamma(2), but not the related PLC beta(2) isoform. Furthermore, in addition to the complex, we report the crystal structures of free spPH and Rac2 bound to GDP and GTP gamma S. These structures illustrate a mechanism of conformational switches that accompany formation of signaling active complexes and highlight the role of effector binding as a common feature of Rac and Cdc42 interactions with a variety of effectors.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User:	Mark Roe
Date Deposited:	06 Feb 2012 20:13
Last Modified:	30 Nov 2012 17:06
URI:	http://sro.sussex.ac.uk/id/eprint/24726

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