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Crystal structure of Rac1 bound to its effector phospholipase C-beta2.
- Source :
-
Nature structural & molecular biology [Nat Struct Mol Biol] 2006 Dec; Vol. 13 (12), pp. 1135-40. Date of Electronic Publication: 2006 Nov 19. - Publication Year :
- 2006
-
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.
- Subjects :
- Crystallography, X-Ray
Humans
Isoenzymes genetics
Models, Molecular
Mutation genetics
Phospholipase C beta
Protein Binding
Protein Structure, Quaternary
Static Electricity
Type C Phospholipases genetics
rac1 GTP-Binding Protein genetics
Isoenzymes chemistry
Isoenzymes metabolism
Type C Phospholipases chemistry
Type C Phospholipases metabolism
rac1 GTP-Binding Protein chemistry
rac1 GTP-Binding Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1545-9993
- Volume :
- 13
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Nature structural & molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 17115053
- Full Text :
- https://doi.org/10.1038/nsmb1175