title: A general mechanism for regulation of access to the translocon: competition for a membrane attachment site on ribosomes.
abstract: For proteins to enter the secretory pathway, the membrane attachment site (M-site) on ribosomes must bind cotranslationally to the Sec61 complex present in the endoplasmic reticulum membrane. The signal recognition particle (SRP) and its receptor (SR) are required for targeting, and the nascent polypeptide associated complex (NAC) prevents inappropriate targeting of nonsecretory nascent chains. In the absence of NAC, any ribosome, regardless of the polypeptide being synthesized, binds to the endoplasmic reticulum membrane, and even nonsecretory proteins are translocated across the endoplasmic reticulum membrane. By occupying the M-site, NAC prevents all ribosome binding unless a signal peptide and SRP are present. The mechanism by which SRP overcomes the NAC block is unknown. We show that signal peptide-bound SRP occupies the M-site and therefore keeps it free of NAC. To expose the M-site and permit ribosome binding, SR can pull SRP away from the M-site without prior release of SRP from the signal peptide.
authors.affiliation: Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: I
authors.initials: I
authors.lastname: Möller
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: B
authors.initials: B
authors.lastname: Beatrix
authors.forename: R
authors.initials: R
authors.lastname: Levy
authors.forename: G
authors.initials: G
authors.lastname: Kreibich
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: M
authors.initials: M
authors.lastname: Wiedmann
authors.forename: B
authors.initials: B
authors.lastname: Lauring
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D018832:Molecular Chaperones; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism*; D000069816:SEC Translocation Channels; D018271:Signal Recognition Particle / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D018832:Molecular Chaperones; D000069816:SEC Translocation Channels; D018271:Signal Recognition Particle; D015534:Trans-Activators; C096099:nascent-polypeptide-associated complex