Egea Pascal F, Stroud Robert M, Walter Peter
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
Curr Opin Struct Biol. 2005 Apr;15(2):213-20. doi: 10.1016/j.sbi.2005.03.007.
In all three kingdoms of life, co-translational targeting of secretory and membrane proteins to the prokaryotic plasma membrane or eukaryotic endoplasmic reticulum is mediated by a ribonucleoprotein complex, the signal recognition particle (SRP), and its membrane-associated receptor (SR). SRP binds to signal sequences of nascent proteins as they emerge from the exit tunnel of the ribosome. The resulting targeting complex, composed of the SRP and the ribosome-nascent chain complex (RNC), then docks with the SR in a GTP-dependent manner. Passing through a complex series of conformational states, SRP and SR deliver the RNC to the translocon, which in turn mediates protein translocation across or integration into the membrane. The core structural and mechanistic principles of SRP-dependent protein targeting are universally conserved. Recent structural investigations combining X-ray crystallography and cryo-electron microscopy have provided new insights into three essentials steps of the SRP-dependent protein targeting cycle: the assembly and interaction of the SRP ribonucleoprotein core, the GTP-dependent SRP-SR association, and the interaction between SRP and the ribosome.
在生命的三个界中，分泌蛋白和膜蛋白共翻译靶向原核生物的质膜或真核生物的内质网是由一种核糖核蛋白复合体——信号识别颗粒（SRP）及其膜相关受体（SR）介导的。当新生蛋白质的信号序列从核糖体的出口通道出现时，SRP会与之结合。由此产生的靶向复合体由SRP和核糖体-新生链复合体（RNC）组成，然后以GTP依赖的方式与SR对接。通过一系列复杂的构象状态，SRP和SR将RNC递送至易位子，易位子进而介导蛋白质跨膜转运或整合到膜中。SRP依赖的蛋白质靶向的核心结构和机制原理是普遍保守的。最近结合X射线晶体学和冷冻电子显微镜的结构研究为SRP依赖的蛋白质靶向循环的三个基本步骤提供了新的见解：SRP核糖核蛋白核心的组装和相互作用、GTP依赖的SRP-SR结合以及SRP与核糖体之间的相互作用。
