title: tRNA acceptor stem and anticodon bases form independent codes related to protein folding.
abstract: Aminoacyl-tRNA synthetases recognize tRNA anticodon and 3' acceptor stem bases. Synthetase Urzymes acylate cognate tRNAs even without anticodon-binding domains, in keeping with the possibility that acceptor stem recognition preceded anticodon recognition. Representing tRNA identity elements with two bits per base, we show that the anticodon encodes the hydrophobicity of each amino acid side-chain as represented by its water-to-cyclohexane distribution coefficient, and this relationship holds true over the entire temperature range of liquid water. The acceptor stem codes preferentially for the surface area or size of each side-chain, as represented by its vapor-to-cyclohexane distribution coefficient. These orthogonal experimental properties are both necessary to account satisfactorily for the exposed surface area of amino acids in folded proteins. Moreover, the acceptor stem codes correctly for β-branched and carboxylic acid side-chains, whereas the anticodon codes for a wider range of such properties, but not for size or β-branching. These and other results suggest that genetic coding of 3D protein structures evolved in distinct stages, based initially on the size of the amino acid and later on its compatibility with globular folding in water.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260 carter@med.unc.edu water@med.unc.edu.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Carter
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260 carter@med.unc.edu water@med.unc.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Wolfenden
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D000926:Anticodon / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D019143:Evolution, Molecular; D005815:Genetic Code; D057927:Hydrophobic and Hydrophilic Interactions; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D017510:Protein Folding; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D013816:Thermodynamics
chemical_list: D000926:Anticodon; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases
keywords: aminoacyl-tRNA synthetases; genetic code; multivariate regression; protein folding; urzymes