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- Title
Crystal structure of Rac1 bound to its effector phospholipase C-beta2.
- Authors
Jezyk, Mark R; Snyder, Jason T; Gershberg, Svetlana; Worthylake, David K; Harden, T Kendall; Sondek, John
- Abstract
Although diverse signaling cascades require the coordinated regulation of heterotrimeric G proteins and small GTPases, these connections remain poorly understood. We present the crystal structure of the GTPase Rac1 bound to phospholipase C-beta2 (PLC-beta2), a classic effector of heterotrimeric G proteins. Rac1 engages the pleckstrin-homology (PH) domain of PLC-beta2 to optimize its orientation for substrate membranes. Gbetagamma also engages the PH domain to activate PLC-beta2, and these two activation events are compatible, leading to additive stimulation of phospholipase activity. In contrast to PLC-delta, the PH domain of PLC-beta2 cannot bind phosphoinositides, eliminating this mode of regulation. The structure of the Rac1-PLC-beta2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, and substitutions within PLC-beta2 abrogate its stimulation by Rac1 but not by Gbetagamma, allowing for functional dissection of this integral signaling node.
- Publication
Nature structural & molecular biology, 2006, Vol 13, Issue 12, p1135
- ISSN
1545-9993
- Publication type
Journal Article
- DOI
10.1038/nsmb1175