Lütcke H
Zentrum für Molekulare Biologie Heidelberg (ZMBH), Germany.
Eur J Biochem. 1995 Mar 15;228(3):531-50. doi: 10.1111/j.1432-1033.1995.tb20293.x.
In higher eukaryotes, most secretory and membrane proteins are synthesised by ribosomes which are attached to the membrane of the rough endoplasmic reticulum (RER). This allows the proteins to be translocated across that membrane already during their synthesis. The ribosomes are directed to the RER membrane by a cytoplasmic ribonucleoprotein particle, the signal recognition particle (SRP). SRP fulfills its task by virtue of three distinguishable activities: the binding of a signal sequence which, being part of the nascent polypeptide to be translocated, is exposed on the surface of a translating ribosome; the retardation of any further elongation; and the SRP-receptor-mediated binding of the complex of ribosome, nascent polypeptide and SRP to the RER membrane which results in the detachment of SRP from the signal sequence and the ribosome and the insertion of the nascent polypeptide into the membrane. Evidence is accumulating that SRP is not restricted to eukaryotes: SRP-related particles and SRP-receptor-related molecules are found ubiquitously and may function in protein translocation in every living organism. This review focuses on the mammalian SRP. A brief discussion of its overall structure is followed by a detailed description of the structures of its RNA and protein constituents and the requirements for their assembly into the particle. Homologues of SRP components from organisms other than mammals are mentioned to emphasize the components' conserved or less conserved features. Subsequently, the functions of each of the SRP constituents are discussed. This sets the stage for a presentation of a model for the mechanism by which SRP cyclically assembles and disassembles with translating ribosomes and the RER membrane. It may be expected that similar mechanisms are used by SRP homologues in organisms other than mammals. However, the mammalian SRP-mediated translocation mechanism may not be conserved in its entirety in organisms like Escherichia coli whose SRP lack components required for the function of the mammalian SRP. Possible translocation pathways involving the rudimentary SRP are discussed in view of the existence of alternative, chaperone-mediated translocation pathways with which they may intersect. The concluding two sections deal with open questions in two areas of SRP research. One formulates basic questions regarding the little-investigated biogenesis of SRP. The other gives an outlook over the insights into the mechanisms of each of the known activities of the SRP that are to be expected in the short and medium-term future.
在高等真核生物中，大多数分泌蛋白和膜蛋白是由附着在内质网（RER）膜上的核糖体合成的。这使得蛋白质在合成过程中就能穿过该膜进行转运。核糖体通过一种细胞质核糖核蛋白颗粒——信号识别颗粒（SRP）被引导至RER膜。SRP凭借三种可区分的活性完成其任务：结合信号序列，该序列作为待转运新生多肽的一部分，暴露在正在翻译的核糖体表面；抑制任何进一步的延伸；以及SRP受体介导的核糖体、新生多肽和SRP复合物与RER膜的结合，这导致SRP从信号序列和核糖体上脱离，以及新生多肽插入膜中。越来越多的证据表明，SRP并不局限于真核生物：与SRP相关的颗粒和与SRP受体相关的分子普遍存在，并且可能在每个生物体的蛋白质转运中发挥作用。本综述聚焦于哺乳动物的SRP。首先简要讨论其整体结构，随后详细描述其RNA和蛋白质成分的结构以及它们组装成颗粒的要求。提及了来自非哺乳动物生物体的SRP成分的同源物，以强调这些成分的保守或不太保守的特征。随后，讨论了SRP各成分的功能。这为呈现SRP与正在翻译的核糖体和RER膜周期性组装和解离的机制模型奠定了基础。可以预期，非哺乳动物生物体中的SRP同源物会使用类似的机制。然而，哺乳动物的SRP介导的转运机制在大肠杆菌等生物体中可能并非完全保守，因为大肠杆菌的SRP缺乏哺乳动物SRP功能所需的成分。鉴于存在可能与之交叉的替代的、伴侣介导的转运途径，讨论了涉及基本SRP的可能转运途径。最后两节讨论了SRP研究两个领域中的未解决问题。一节提出了关于研究较少的SRP生物发生的基本问题。另一节展望了在短期和中期未来有望获得的对SRP已知各项活性机制的见解。
