Crystal structure of Rac1 bound to its effector phospholipase C-β2
Crystal structure of Rac1 bound to its effector phospholipase C-β2
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DOI：
10.1038/nsmb1175
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发表时间：
2006-12-01
影响因子：
16.8
通讯作者：
Sondek, John
中科院分区：
文献类型：
--
作者：
Jezyk, Mark R.;Snyder, Jason T.;Sondek, John
虽然不同的信号级联需要异源三聚体G蛋白和小GTP酶的协调调节，这些连接仍然知之甚少。我们目前的晶体结构的GTCRac 1结合磷脂酶C-β 2（PLC-β 2），一个典型的异源三聚体G蛋白的效应。Rac 1与PLC-β 2的普列克底物蛋白同源（PH）结构域结合，以优化其对基底膜的定向。G beta gamma也参与PH结构域以激活PLC-β 2，并且这两个激活事件是相容的，导致磷脂酶活性的叠加刺激。与PLC-δ相反，PLC-β 2的PH结构域不能结合磷酸肌醇，消除了这种调节模式。Rac 1-PLC-β 2复合物的结构揭示了决定PLC-β同工酶对Rac GTP酶的选择性超过其他Rho家族GTP酶的决定因素，PLC-β 2内的取代消除了Rac 1而不是G β γ的刺激，从而允许对该整合信号节点进行功能性解剖。
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-beta 2 (PLC-beta 2), a classic effector of heterotrimeric G proteins. Rac1 engages the pleckstrin-homology (PH) domain of PLC-beta 2 to optimize its orientation for substrate membranes. G beta gamma also engages the PH domain to activate PLC-beta 2, and these two activation events are compatible, leading to additive stimulation of phospholipase activity. In contrast to PLC-delta, the PH domain of PLC-beta 2 cannot bind phosphoinositides, eliminating this mode of regulation. The structure of the Rac1-PLC-beta 2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, and substitutions within PLC-beta 2 abrogate its stimulation by Rac1 but not by G beta gamma, allowing for functional dissection of this integral signaling node.