title: Analysis of the interplay of protein biogenesis factors at the ribosome exit site reveals new role for NAC.
abstract: The ribosome exit site is a focal point for the interaction of protein-biogenesis factors that guide the fate of nascent polypeptides. These factors include chaperones such as NAC, N-terminal-modifying enzymes like Methionine aminopeptidase (MetAP), and the signal recognition particle (SRP), which targets secretory and membrane proteins to the ER. These factors potentially compete with one another in the short time-window when the nascent chain first emerges at the exit site, suggesting a need for regulation. Here, we show that MetAP contacts the ribosome at the universal adaptor site where it is adjacent to the α subunit of NAC. SRP is also known to contact the ribosome at this site. In the absence of NAC, MetAP and SRP antagonize each other, indicating a novel role for NAC in regulating the access of MetAP and SRP to the ribosome. NAC also functions in SRP-dependent targeting and helps to protect substrates from aggregation before translocation.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Nyathi
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK martin.r.pool@manchester.ac.uk.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pool
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology*; D014176:Protein Biosynthesis; D021381:Protein Transport; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D018271:Signal Recognition Particle / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C097165:EGD2 protein, S cerevisiae; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle; C096099:nascent-polypeptide-associated complex; D000626:Aminopeptidases