The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane.
The signal recognition particle receptor (SR) is required for the cotranslational targeting of both secretory and membrane proteins to the endoplasmic reticulum (ER) membrane. During targeting, the SR interacts with the signal recognition particle (SRP) which is bound to the signal sequence of the nascent protein chain. This interaction catalyzes the GTP-dependent transfer of the nascent chain from SRP to the protein translocation apparatus in the ER membrane. The SR is a heterodimeric protein comprised of a 69-kD subunit (SR alpha) and a 30-kD subunit (SR beta) which are associated with the ER membrane in an unknown manner. SR alpha and the 54-kD subunits of SRP (SRP54) each contain related GTPase domains which are required for SR and SRP function. Molecular cloning and sequencing of a cDNA encoding SR beta revealed that SR beta is a transmembrane protein and, like SR alpha and SRP54, is a member of the GTPase superfamily. Although SR beta defines its own GTPase subfamily, it is distantly related to ARF and Sar1. Using UV cross-linking, we confirm that SR beta binds GTP specifically. Proteolytic digestion experiments show that SR alpha is required for the interaction of SRP with SR. SR alpha appears to be peripherally associated with the ER membrane, and we suggest that SR beta, as an integral membrane protein, mediates the membrane association of SR alpha. The discovery of its guanine nucleotide-binding domain, however, makes it likely that its role is more complex than that of a passive anchor for SR alpha. These findings suggest that a cascade of three directly interacting GTPases functions during protein targeting to the ER membrane.
Miller
J D
JD
Department of Biochemistry and Biophysics, University of California Medical School, San Francisco 94143-0448.
Tajima
S
S
Lauffer
L
L
Walter
P
P
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D007425:Intracellular Membranes / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D018271:Signal Recognition Particle / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C503637:Srp72 protein, mouse; C036318:signal peptide receptor; D020558:GTP Phosphohydrolases