Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex.
Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex.
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DOI：
10.1126/science.1193438
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发表时间：
2010-11-12
期刊：
影响因子：
--
通讯作者：
Harden TK
中科院分区：
文献类型：
--
作者：
Waldo GL;Ricks TK;Hicks SN;Cheever ML;Kawano T;Tsuboi K;Wang X;Montell C;Kozasa T;Sondek J;Harden TK
由广泛的细胞外刺激引发的跨膜信号会聚在调节磷脂酶C（PLC）依赖的肌醇脂质水解的节点上进行信号传播。我们描述了异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）如何激活PLC-βs，并反过来被这些下游效应物灭活。与活化Gαq结合的PLC-β3的2.7埃结构揭示了在PLC-βs和其他效应物中发现的保守模块，这些效应物被优化用于活化G蛋白的快速接合。PLC-β3在复合物中的活性位点被分子内塞封闭，该分子内塞可能在G蛋白依赖性的脂肪酶在膜表面的锚定和定向后被去除。PLC-β3的第二个结构域随后通过Gαq加速鸟苷三磷酸水解，导致复合物解离并终止信号传播。该结构域内的突变在体外和体内显著延迟信号终止。因此，这项工作提出了一个动态的捕捉和释放机制，用于锐化时空信号介导的不同的感觉输入。
Transmembrane signals initiated by a broad range of extracellular stimuli converge on nodes that regulate phospholipase C (PLC)–dependent inositol lipid hydrolysis for signal propagation. We describe how heterotrimeric guanine nucleotide–binding proteins (G proteins) activate PLC-βs and in turn are deactivated by these downstream effectors. The 2.7-angstrom structure of PLC-β3 bound to activated Gαq reveals a conserved module found within PLC-βs and other effectors optimized for rapid engagement of activated G proteins. The active site of PLC-β3 in the complex is occluded by an intramolecular plug that is likely removed upon G protein–dependent anchoring and orientation of the lipase at membrane surfaces. A second domain of PLC-β3 subsequently accelerates guanosine triphosphate hydrolysis by Gαq, causing the complex to dissociate and terminate signal propagation. Mutations within this domain dramatically delay signal termination in vitro and in vivo. Consequently, this work suggests a dynamic catch-and-release mechanism used to sharpen spatiotemporal signals mediated by diverse sensory inputs.
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影响因子：
56.9
作者：
SMRCKA, AV;HEPLER, JR;STERNWEIS, PC
通讯作者：
STERNWEIS, PC
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
影响因子：
56.9
作者：
Lutz, Susanne;Shankaranarayanan, Aruna;Tesmer, John J. G.
通讯作者：
Tesmer, John J. G.
影响因子：
4.8
作者：
Skiba, NP;Hopp, JA;Arshavsky, VY
通讯作者：
Arshavsky, VY
影响因子：
16
作者：
Hicks SN;Jezyk MR;Gershburg S;Seifert JP;Harden TK;Sondek J
通讯作者：
Sondek J