title: The mechanics of translocation: a molecular "spring-and-ratchet" system.
abstract: The translation of genetic information into proteins is a fundamental process of life. Stepwise addition of amino acids to the growing polypeptide chain requires the coordinated movement of mRNA and tRNAs through the ribosome, a process known as translocation. Here, we review current understanding of the kinetics and mechanics of translocation, with particular emphasis on the structure of a functional mammalian ribosome stalled during translocation by an mRNA pseudoknot. In the context of a pseudoknot-stalled complex, the translocase EF-2 is seen to compress a hybrid-state tRNA into a strained conformation. We propose that this strain energy helps overcome the kinetic barrier to translocation and drives tRNA into the P-site, with EF-2 biasing this relaxation in one direction. The tRNA can thus be considered a molecular spring and EF-2 a Brownian ratchet in a "spring-and-ratchet" system within the translocation process.
authors.affiliation: Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moran
authors.forename: John F
authors.initials: JF
authors.lastname: Flanagan
authors.forename: Olivier
authors.initials: O
authors.lastname: Namy
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
authors.forename: Ian
authors.initials: I
authors.lastname: Brierley
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D007700:Kinetics; D008322:Mammals; D008958:Models, Molecular; D009068:Movement; D009690:Nucleic Acid Conformation; D020652:Peptide Elongation Factor 2 / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D020652:Peptide Elongation Factor 2; D012333:RNA, Messenger; D012343:RNA, Transfer