title: A GTPase cycle in initiation of protein translocation across the endoplasmic reticulum membrane.
abstract: In higher eukaryotes proteins bearing a signal sequence are translocated across the membrane of the endoplasmic reticulum (ER). The initial events of protein translocation are the binding of the signal sequence by the 54 kDa subunit (SRP54) of the signal recognition particle (SRP) and the targeting of the ribosome nascent chain complex to the ER. Targeting is mediated by the binding of SRP to the SRP receptor, a membrane protein comprising two different subunits, SR alpha and SR beta. Interaction of SRP and SR alpha/SR beta causes release of the signal and the engagement of the nascent chain with the membrane-bound translocation apparatus. Both SRP54 and SR alpha contain homologous domains which include a predicted GTPase fold. The transmembrane protein SR beta also contains a GTPase domain, but it is not closely related to those of SRP54 and SR alpha. All three proteins bind GTP specifically, and the SR alpha/SR beta complex stimulates both GTP binding to and GTP hydrolysis by SRP54. We suggest a model for the initiation of protein translocation across the ER in which SR alpha beta catalyses a cycle of GTP binding, hydrolysis and release by SRP54 that regulates its dissociation from the signal sequence.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco 94143-0448.
authors.forename: J D
authors.initials: JD
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Walter
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology; D011506:Proteins / Q000378:metabolism*
chemical_list: D021382:Protein Sorting Signals; D011506:Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins