title: Indirect readout of tRNA for aminoacylation.
abstract: Aminoacylation of tRNA by aminoacyl-tRNA synthetases is the essential reaction that matches protein amino acids with the trinucleotide sequences specified in mRNA. Direct electrostatic interactions made by tRNA synthetases with discriminating functional groups on the tRNA bases have long been known to determine aminoacylation specificity. However, structural and biochemical studies have revealed a second "indirect readout" mechanism that makes an important contribution as well. In indirect readout, the sequence-dependent conformations of tRNA are recognized through protein contacts with the sugar-phosphate backbone and with nonspecific portions of the bases. This mechanism appears to function in single-stranded regions, in canonical A-type duplex segments, and in the complex tertiary core portion of the tRNA. Operation of the indirect mechanism is not exclusive of the direct mechanism, and both are further mediated by induced-fit rearrangements, in which enzyme and tRNA undergo precise conformational changes after formation of an initial encounter complex. The examples of indirect readout in tRNA synthetase complexes extend the concept beyond its traditional application to DNA duplexes and serve as models for the operation of this mechanism in more complex systems such as the ribosome.
authors: Department of Chemistry and Biochemistry and Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, California 93106-9510, USA. perona@chem.ucsb.edu
authors: John J
authors: JJ
authors: Perona
authors: Ya-Ming
authors: YM
authors: Hou
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D001483:Base Sequence; D002384:Catalysis; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046249:Transfer RNA Aminoacylation
chemical_list: D009692:Nucleic Acid Heteroduplexes; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases