title: Structural insights into translational fidelity.
abstract: The underlying basis for the accuracy of protein synthesis has been the subject of over four decades of investigation. Recent biochemical and structural data make it possible to understand at least in outline the structural basis for tRNA selection, in which codon recognition by cognate tRNA results in the hydrolysis of GTP by EF-Tu over 75 A away. The ribosome recognizes the geometry of codon-anticodon base pairing at the first two positions but monitors the third, or wobble position, less stringently. Part of the additional binding energy of cognate tRNA is used to induce conformational changes in the ribosome that stabilize a transition state for GTP hydrolysis by EF-Tu and subsequently result in accelerated accommodation of tRNA into the peptidyl transferase center. The transition state for GTP hydrolysis is characterized, among other things, by a distorted tRNA. This picture explains a large body of data on the effect of antibiotics and mutations on translational fidelity. However, many fundamental questions remain, such as the mechanism of activation of GTP hydrolysis by EF-Tu, and the relationship between decoding and frameshifting.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom. james.ogle@cantab.net
authors.forename: James M
authors.initials: JM
authors.lastname: Ogle
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020029:Base Pairing; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007700:Kinetics; D008957:Models, Genetic; D008958:Models, Molecular; D009154:Mutation; D014176:Protein Biosynthesis / Q000187:drug effects; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012343:RNA, Transfer