title: Regulation by a chaperone improves substrate selectivity during cotranslational protein targeting.
abstract: The ribosome exit site is a crowded environment where numerous factors contact nascent polypeptides to influence their folding, localization, and quality control. Timely and accurate selection of nascent polypeptides into the correct pathway is essential for proper protein biogenesis. To understand how this is accomplished, we probe the mechanism by which nascent polypeptides are accurately sorted between the major cotranslational chaperone trigger factor (TF) and the essential cotranslational targeting machinery, signal recognition particle (SRP). We show that TF regulates SRP function at three distinct stages, including binding of the translating ribosome, membrane targeting via recruitment of the SRP receptor, and rejection of ribosome-bound nascent polypeptides beyond a critical length. Together, these mechanisms enhance the specificity of substrate selection into both pathways. Our results reveal a multilayered mechanism of molecular interplay at the ribosome exit site, and provide a conceptual framework to understand how proteins are selected among distinct biogenesis machineries in this crowded environment.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Aileen
authors.initials: A
authors.lastname: Ariosa
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Ishu
authors.initials: I
authors.lastname: Saraogi
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 sshan@caltech.edu.
authors.forename: Shu-ou
authors.initials: SO
authors.lastname: Shan
mesh_terms: D000595:Amino Acid Sequence; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D018832:Molecular Chaperones; D011506:Proteins; D018271:Signal Recognition Particle
keywords: GTPases; protein biogenesis; ribosome; signal recognition particle; trigger factor