Crystal structure of Rac1 bound to its effector phospholipase C-β2
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-β2 (PLC-β2), a classic effector of heterotrimeric G proteins...
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| Veröffentlicht in: | Nature structural & molecular biology 2006-12, Vol.13 (12), p.1135-1140 |
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| container_issue | 12 |
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| container_title | Nature structural & molecular biology |
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| creator | Sondek, John Jezyk, Mark R Snyder, Jason T Gershberg, Svetlana Worthylake, David K Harden, T Kendall |
| description | 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-β2 (PLC-β2), a classic effector of heterotrimeric G proteins. Rac1 engages the pleckstrin-homology (PH) domain of PLC-β2 to optimize its orientation for substrate membranes. Gβγ also engages the PH domain to activate PLC-β2, and these two activation events are compatible, leading to additive stimulation of phospholipase activity. In contrast to PLC-δ, the PH domain of PLC-β2 cannot bind phosphoinositides, eliminating this mode of regulation. The structure of the Rac1–PLC-β2 complex reveals determinants that dictate selectivity of PLC-β isozymes for Rac GTPases over other Rho-family GTPases, and substitutions within PLC-β2 abrogate its stimulation by Rac1 but not by Gβγ, allowing for functional dissection of this integral signaling node. |
| doi_str_mv | 10.1038/nsmb1175 |
| format | Article |
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| source | Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Biochemistry Biological Microscopy Biomedical and Life Sciences Cellular signal transduction Life Sciences Membrane Biology Neurotransmitters Phospholipases Physiological aspects Protein Structure Structure |
| title | Crystal structure of Rac1 bound to its effector phospholipase C-β2 |
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