title: The ribosome regulates the GTPase of the beta-subunit of the signal recognition particle receptor.
abstract: Protein targeting to the membrane of the ER is regulated by three GTPases, the 54-kD subunit of the signal recognition particle (SRP) and the alpha- and beta-subunit of the SRP receptor (SR). Here, we report on the GTPase cycle of the beta-subunits of the SR (SRbeta). We found that SRbeta binds GTP with high affinity and interacts with ribosomes in the GTP-bound state. Subsequently, the ribosome increases the GTPase activity of SRbeta and thus functions as a GTPase activating protein for SRbeta. Furthermore, the interaction between SRbeta and the ribosome leads to a reduction in the affinity of SRbeta for guanine nucleotides. We propose that SRbeta regulates the interaction of SR with the ribosome and thereby allows SRalpha to scan membrane-bound ribosomes for the presence of SRP. Interaction between SRP and SRalpha then leads to release of the signal sequence from SRP and insertion into the translocon. GTP hydrolysis then results in dissociation of SR from the ribosome, and SRP from the SR.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, D-69052 Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Bacher
authors.forename: M
authors.initials: M
authors.lastname: Pool
authors.forename: B
authors.initials: B
authors.lastname: Dobberstein
mesh_terms: D000818:Animals; D001665:Binding Sites; D004285:Dogs; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006868:Hydrolysis; D008081:Liposomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008861:Microsomes; D008954:Models, Biological; D018832:Molecular Chaperones; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D000069816:SEC Translocation Channels; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D008081:Liposomes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D000069816:SEC Translocation Channels; D015534:Trans-Activators; C096099:nascent-polypeptide-associated complex; C036318:signal peptide receptor; C074282:translocating chain-associating membrane protein (TRAM); D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases