Substrate twinning activates the signal recognition particle and its receptor
Substrate twinning activates the signal recognition particle and its receptor
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DOI：
10.1038/nature02250
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发表时间：
2004-01-15
期刊：
影响因子：
64.8
通讯作者：
Stroud, RM
中科院分区：
文献类型：
--
作者：
Egea, PF;Shan, SO;Stroud, RM
信号序列靶向蛋白质以从细胞分泌或整合到细胞膜中。当新生蛋白质从核糖体中出现时，信号序列被信号识别颗粒（SRP）识别，随后与其受体（SR）结合。在该复合物中，SRP和SR刺激彼此的GTP酶活性，并且GTP水解确保通过膜中的易位孔单向靶向货物。为了确定相互激活的机制，我们确定了这两个GTP酶之间形成的复合物的1.9埃结构。这两个伴侣形成准双重对称的异二聚体。生化分析支持广泛的相互作用表面的重要性。复合物的形成将两个GTP分子排列在对称的复合活性位点中，并且3' OH基团对于缔合、相互激活和催化是必不可少的。这种独特的孪生相互作用循环在水解时被切断两次，导致货物递送后的复杂解离。
Signal sequences target proteins for secretion from cells or for integration into cell membranes. As nascent proteins emerge from the ribosome, signal sequences are recognized by the signal recognition particle (SRP), which subsequently associates with its receptor (SR). In this complex, the SRP and SR stimulate each other's GTPase activity, and GTP hydrolysis ensures unidirectional targeting of cargo through a translocation pore in the membrane. To define the mechanism of reciprocal activation, we determined the 1.9 Angstrom structure of the complex formed between these two GTPases. The two partners form a quasi-two-fold symmetrical heterodimer. Biochemical analysis supports the importance of the extensive interaction surface. Complex formation aligns the two GTP molecules in a symmetrical, composite active site, and the 3' OH groups are essential for association, reciprocal activation and catalysis. This unique circle of twinned interactions is severed twice on hydrolysis, leading to complex dissociation after cargo delivery.