2FJU

Activated Rac1 bound to its effector phospholipase C beta 2

Summary for 2FJU

• Entry DOI: 10.2210/pdb2fju/pdb
• Descriptor: Ras-related C3 botulinum toxin substrate 1, 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta 2, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: protein-protein complex, signaling protein, apoptosis-hydrolase complex, apoptosis/hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000
• Total number of polymer chains: 2
• Total formula weight: 111435.39

Authors

Jezyk, M.R.,Snyder, J.T.,Harden, T.K.,Sondek, J. (deposition date: 2006-01-03, release date: 2006-11-21, Last modification date: 2024-02-14)

Primary citation

Jezyk, M.R.,Snyder, J.T.,Gershberg, S.,Worthylake, D.K.,Harden, T.K.,Sondek, J.
Crystal structure of Rac1 bound to its effector phospholipase C-beta2.
Nat.Struct.Mol.Biol., 13:1135-1140, 2006

PubMed 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.

PubMed: 17115053
DOI: 10.1038/nsmb1175

Experimental method

X-RAY DIFFRACTION (2.2 Å)