title: Ribosome. Mechanical force releases nascent chain-mediated ribosome arrest in vitro and in vivo.
abstract: Protein synthesis rates can affect gene expression and the folding and activity of the translation product. Interactions between the nascent polypeptide and the ribosome exit tunnel represent one mode of regulating synthesis rates. The SecM protein arrests its own translation, and release of arrest at the translocon has been proposed to occur by mechanical force. Using optical tweezers, we demonstrate that arrest of SecM-stalled ribosomes can indeed be rescued by force alone and that the force needed to release stalling can be generated in vivo by a nascent chain folding near the ribosome tunnel exit. We formulate a kinetic model describing how a protein can regulate its own synthesis by the force generated during folding, tuning ribosome activity to structure acquisition by a nascent polypeptide.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Goldman
authors.affiliation: Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA. Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA. carlos@alice.berkeley.edu kaiser@jhu.edu.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Kaiser
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA. Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Milin
authors.affiliation: Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Righini
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Tinoco
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA. Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA. Department of Physics, University of California, Berkeley, CA 94720, USA. Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Kavli Energy Nanosciences Institute at Berkeley, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. carlos@alice.berkeley.edu kaiser@jhu.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bustamante
mesh_terms: D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D066298:In Vitro Techniques; D007700:Kinetics; D055595:Mechanical Phenomena; D052898:Optical Tweezers; D010441:Peptide Chain Elongation, Translational; D017510:Protein Folding; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; C497347:SecM protein, E coli; D014157:Transcription Factors