Signal recognition particle (SRP), a ubiquitous initiator of protein translocation.

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.