title: Binding of signal recognition particle gives ribosome/nascent chain complexes a competitive advantage in endoplasmic reticulum membrane interaction.
abstract: Most secretory and membrane proteins are sorted by signal sequences to the endoplasmic reticulum (ER) membrane early during their synthesis. Targeting of the ribosome-nascent chain complex (RNC) involves the binding of the signal sequence to the signal recognition particle (SRP), followed by an interaction of ribosome-bound SRP with the SRP receptor. However, ribosomes can also independently bind to the ER translocation channel formed by the Sec61p complex. To explain the specificity of membrane targeting, it has therefore been proposed that nascent polypeptide-associated complex functions as a cytosolic inhibitor of signal sequence- and SRP-independent ribosome binding to the ER membrane. We report here that SRP-independent binding of RNCs to the ER membrane can occur in the presence of all cytosolic factors, including nascent polypeptide-associated complex. Nontranslating ribosomes competitively inhibit SRP-independent membrane binding of RNCs but have no effect when SRP is bound to the RNCs. The protective effect of SRP against ribosome competition depends on a functional signal sequence in the nascent chain and is also observed with reconstituted proteoliposomes containing only the Sec61p complex and the SRP receptor. We conclude that cytosolic factors do not prevent the membrane binding of ribosomes. Instead, specific ribosome targeting to the Sec61p complex is provided by the binding of SRP to RNCs, followed by an interaction with the SRP receptor, which gives RNC-SRP complexes a selective advantage in membrane targeting over nontranslating ribosomes.
authors.affiliation: Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Neuhof
authors.forename: M M
authors.initials: MM
authors.lastname: Rolls
authors.forename: B
authors.initials: B
authors.lastname: Jungnickel
authors.forename: K U
authors.initials: KU
authors.lastname: Kalies
authors.forename: T A
authors.initials: TA
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D018832:Molecular Chaperones; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000502:physiology; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D012156:Reticulocytes / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism* / Q000502:physiology; D018271:Signal Recognition Particle / Q000378:metabolism* / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators
chemical_list: D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D011506:Proteins; D018271:Signal Recognition Particle; D015534:Trans-Activators; C096099:nascent-polypeptide-associated complex