Egea Pascal F, Shan Shu-Ou, Napetschnig Johanna, Savage David F, Walter Peter, Stroud Robert M
Department of Biochemistry and Biophysics, University of California at San Francisco, California 94143-2240, USA.
Nature. 2004 Jan 15;427(6971):215-21. doi: 10.1038/nature02250.
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 A 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.
信号序列引导蛋白质从细胞中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SRP与其受体（SR）结合。在这个复合物中，SRP和SR相互刺激对方的GTP酶活性，GTP水解确保货物通过膜上的转运孔单向靶向运输。为了确定相互激活的机制，我们确定了这两种GTP酶之间形成的复合物的1.9埃结构。这两个伙伴形成了一个准二重对称异二聚体。生化分析支持了广泛相互作用表面的重要性。复合物的形成使两个GTP分子在一个对称的复合活性位点上排列，3'OH基团对于结合、相互激活和催化至关重要。这种独特的孪生相互作用循环在水解时被切断两次，导致货物递送后复合物解离。
