title: Unregulated exposure of the ribosomal M-site caused by NAC depletion results in delivery of non-secretory polypeptides to the Sec61 complex.
abstract: Nascent polypeptide associated complex (NAC) interacts with nascent polypeptides emerging from ribosomes. Both signal recognition particle (SRP) and NAC work together to ensure specificity in co-translational targeting by competing for binding to the ribosomal membrane attachment site. While SRP selects signal-containing ribosomes for targeting, NAC prevents targeting of signal peptide-less nascent chains to the endoplasmic reticulum membrane. Here we show that the ribosome binding that occurs in NAC's absence delivers signalless nascent chains to the Sec61 complex, underscoring the danger of unregulated exposure of the ribosomal M-site. Recently, the idea that NAC prevents ribosome binding has been challenged. By carefully examining the physiologic NAC concentration in a variety of tissues from different species we here demonstrate that the discrepancy resulted from subphysiologic NAC concentrations.
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: B
authors.initials: B
authors.lastname: Beatrix
authors.forename: G
authors.initials: G
authors.lastname: Kreibich
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: B
authors.initials: B
authors.lastname: Lauring
authors.forename: M
authors.initials: M
authors.lastname: Wiedmann
mesh_terms: D000818:Animals; D002417:Cattle; D002474:Cell-Free System; D003001:Cloning, Molecular; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D018832:Molecular Chaperones; D009928:Organ Specificity; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D000069816:SEC Translocation Channels; D018271:Signal Recognition Particle / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014908:Triticum
chemical_list: D008565:Membrane Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000069816:SEC Translocation Channels; D018271:Signal Recognition Particle; D015534:Trans-Activators; C096099:nascent-polypeptide-associated complex