tRNA acceptor stem and anticodon bases form independent codes related to protein folding

• Published in: Proceedings of the National Academy of Sciences - PNAS 2015-06, Vol.112 (24), p.7489-7494
• Main Authors: Carter, Charles W, Richard Wolfenden
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acyl-tRNA Synthetases - metabolism; aminoacyl-tRNA synthetases; Anticodon - chemistry; Anticodon - genetics; Anticodon - metabolism; anticodons; Binding Sites - genetics; Biological Sciences; Codes; Evolution, Molecular; Genetic Code; Genetics; Hydrophobic and Hydrophilic Interactions; Models, Genetic; Models, Molecular; multivariate regression; Nucleic Acid Conformation; peptides; physical properties; Physical Sciences; Protein Folding; proteins; Regression Analysis; RNA, Transfer - chemistry; RNA, Transfer - genetics; RNA, Transfer - metabolism; Thermodynamics; Transfer RNA; urzymes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1507569112

Significance The universal genetic code is the earliest point to which we can trace biological inheritance. Earlier work hinted at a relationship between the codon bases and the physical properties of the 20 amino acids that dictate the 3D conformations of proteins in solution. Here, we show that acceptor stems and anticodons, which are at opposite ends of the tRNA molecule, code, respectively, for size and polarity. These two distinct properties of the amino acid side-chains jointly determine their preferred locations in folded proteins. The early appearance of an acceptor stem code based on size, β-branching, and carboxylate groups might have favored the appearance of antiparallel peptides that have been suggested to have a special affinity for RNA. 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.