Structure of Gαq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs
Structure of Gαq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs
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DOI：
10.1126/science.1147554
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发表时间：
2007-12-21
期刊：
影响因子：
56.9
通讯作者：
Tesmer, John J. G.
中科院分区：
文献类型：
--
作者：
Lutz, Susanne;Shankaranarayanan, Aruna;Tesmer, John J. G.
鸟嘌呤核苷酸交换因子p63 RhoGEF是异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）G α（q）的效应物，从而将G α（q）偶联受体（GPCR）与小分子量G蛋白RhoA的活化相连接.我们确定了G α（q）-p63 RhoGEF-RhoA复合物的晶体结构，详细描述了G α（q）与p63 RhoGEF的Db 1和普列克底物蛋白同源（DH和PH）结构域的相互作用。这些相互作用涉及效应子结合位点和G α（q）的C-末端区域，并且似乎减轻PH结构域对催化DH结构域的自身抑制。Trio、Duet和p63 RhoGEF被证明构成了一个G alpha（q）效应子家族，这些效应子似乎在体外和完整细胞中激活RhoA。我们建议，这种结构代表了一个古老的信号转导途径，预计将是重要的一系列生理过程的关键。
The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric guanine nucleotide- binding protein ( G protein) G alpha(q) and thereby links G alpha(q)- coupled receptors ( GPCRs) to the activation of the small- molecular- weight G protein RhoA. We determined the crystal structure of the G alpha(q)-p63RhoGEF- RhoA complex, detailing the interactions of G alpha(q) with the Dbl and pleckstrin homology ( DH and PH) domains of p63RhoGEF. These interactions involve the effector- binding site and the C- terminal region of G alpha(q) and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of G alpha(q) effectors that appear to activate RhoA both in vitro and in intact cells. We propose that this structure represents the crux of an ancient signal transduction pathway that is expected to be important in an array of physiological processes.