title: Structural basis for interaction of a cotranslational chaperone with the eukaryotic ribosome.
abstract: Cotranslational chaperones, ubiquitous in all living organisms, protect nascent polypeptides from aggregation and facilitate their de novo folding. Importantly, emerging data have also suggested that ribosome-associated cotranslational chaperones have active regulatory roles in modulating protein translation. By characterizing the structure of a type of eukaryotic cotranslational chaperone, the ribosome-associated complex (RAC) from Saccharomyces cerevisiae, we show that RAC cross-links two ribosomal subunits, through a single long α-helix, to limit the predominant intersubunit rotation required for peptide elongation. We further demonstrate that any changes in the continuity, length or rigidity of this middle α-helix impair RAC function in vivo. Our results suggest a new mechanism in which RAC directly regulates protein translation by mechanically coupling cotranslational folding with the peptide-elongation cycle, and they lay the foundation for further exploration of regulatory roles of RAC in translation control.
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Chengying
authors.initials: C
authors.lastname: Ma
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Center for Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Center for Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Lei
authors.affiliation: Ministry of Education Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
mesh_terms: D000595:Amino Acid Sequence; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D054657:Ribosome Subunits / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C424445:SSZ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C077019:ZUO1 protein, S cerevisiae