Initial amino acid:codon assignments and strength of codon:anticodon binding

Abstract

AbstractThe ribosome is an entropy trap that brings the 3′-aminoacyl- and 3′-peptidyl-termini of two tRNAs together to enable peptidyl transfer. The two tRNAs are bound through their acceptor stems to the peptidyl-transferase centre of the large ribosomal subunit and through their anticodon loops to mRNA at the subunit interface. The latter interaction involving contiguous anticodon:codon pairing is augmented by interactions with the decoding centre of the small ribosomal subunit. Fine-tuning aligns the termini for optimal interaction of the nucleophilic amino group and electrophilic ester carbonyl group. Reasoning that intrinsic codon:anticodon binding might have been a major contributor to bringing tRNA 3′-termini into proximity at an early stage of ribosomal peptide synthesis, we wondered if primordial amino acids might have been assigned to those codons that bind the corresponding anticodon loops most tightly. By measuring the binding of anticodon stem loops to short oligonucleotides, we determined that family box codon:anticodon pairings are typically tighter than split box codon:anticodon pairings. Furthermore, we find only family box anticodon stem loops can bind two contiguous codons simultaneously. The amino acids assigned to family boxes correspond to those accessible by what has been termed cyanosulfidic chemistry, supporting the contention that these limited amino acids might have been the first used in primordial coded peptide synthesis.Table of Contents (TOC) graphic