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

Abstract

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.