2FJU: Activated Rac1 Bound To Its Effector Phospholipase C Beta 2

Citation:
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.
PDB ID: 2FJUDownload
MMDB ID: 42767
PDB Deposition Date: 2006/1/3
Updated in MMDB: 2006/12
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 2FJU: dimeric; determined by author
Molecular Components in 2FJU
Label Count Molecule
Proteins (2 molecules)
1
Ras-related C3 Botulinum Toxin Substrate 1(Gene symbol: RAC1)
Molecule annotation
1
1-phosphatidylinositol-4,5-bisphosphate Phosphodiesterase Beta 2(Gene symbol: PLCB2)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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