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bioRxiv · 10.1101/2023.12.18.572171

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

Su, M.·Roberts, S. J.·Sutherland, J. D.
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Abstract

The ribosome brings 3'-aminoacyl-tRNA and 3'-peptidyl-tRNAs together to enable peptidyl transfer by binding them in two major ways. Firstly, their anticodon loops are bound to mRNA, itself anchored at the ribosomal subunit interface, by contiguous anticodon:codon pairing augmented by interactions with the decoding centre of the small ribosomal subunit. Secondly, their acceptor stems are bound by the peptidyl transferase centre which aligns the 3'-aminoacyl- and 3'-peptidyl-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 that two family box anticodon stem loops can tightly bind a pair of contiguous codons simultaneously whereas two split box anticodon stem loops cannot. 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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC="FIGDIR/small/572171v2_ufig1.gif" ALT="Figure 1"> View larger version (13K): org.highwire.dtl.DTLVardef@189358aorg.highwire.dtl.DTLVardef@119fbeaorg.highwire.dtl.DTLVardef@e9c764org.highwire.dtl.DTLVardef@21b12c_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Su, M., Roberts, S. J., Sutherland, J. D.. 2023-12-18. Initial amino acid:codon assignments and strength of codon:anticodon binding. https://doi.org/10.1101/2023.12.18.572171

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