2fju
From Proteopedia
Activated Rac1 bound to its effector phospholipase C beta 2
Contents |
Overview
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.
Disease
Known disease associated with this structure: Platelet PLC beta-2 deficiency OMIM:[604114]
About this Structure
2FJU is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of Rac1 bound to its effector phospholipase C-beta2., Jezyk MR, Snyder JT, Gershberg S, Worthylake DK, Harden TK, Sondek J, Nat Struct Mol Biol. 2006 Dec;13(12):1135-40. Epub 2006 Nov 19. PMID:17115053 Page seeded by OCA on Sun May 4 03:58:56 2008
