Fig. 2. Functional cycle of the mammalian SRP. (A) SRP binds through the M domain of SRP54 to the signal sequence of membrane and secretory proteins emerging from the exit site of the large ribosomal subunit. (B) The Alu domain promotes transient arrest of the polypeptide chain elongation through an as yet unknown mechanism. The affinity of SRP54 for GTP increases upon docking of SRP with the ribosome. (C) The RNC–SRP complex diffuses to the ER membrane and docks with the SR mainly through the interaction between SRP54 and SRα in the GTP-bound form. SRβ in the GTP-bound form interacts with the RNC complex and induces the transfer of the signal peptide to the translocon. (D) SRP54 and SRα mutually activate their GTPases, and SRP dissociates from the SR upon hydrolysis of GTP, allowing the elongation of the polypeptide to resume.