Abstract
The ribosome CAR interaction surface behaves like an extension of the decoding center A site and has H-bond interactions with the +1 codon that is next in line to enter the A site. Through molecular dynamics simulations, we investigated the codon sequence specificity of this CAR-mRNA interaction and discovered a strong preference for GCN codons, suggesting that there may be a sequence-dependent layer of translational regulation dependent on the CAR interaction surface. Dissection of the CAR-mRNA interaction through nucleotide substitution experiments showed that the first nucleotide of the +1 codon dominates over the second nucleotide position, consistent with an energetically favorable zipper-like activity that emanates from the A site through the CAR-mRNA interface. The +1 codon/CAR interaction is also affected by the identity of nucleotide 3 of +1 GCN codons which influences the stacking of G and C. Clustering analysis suggests that the A site decoding center adopts different neighborhood substates that depend on the identity of the +1 codon.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
cdalgarno{at}wesleyan.edu (C.D.); kscopino{at}wesleyan.edu (K.S.); mraval{at}wesleyan.edu (M.R.); cnachmanoff{at}wesleyan.edu (C.N.); esakkas{at}wesleyan.edu (E.S.); dkrizanc{at}wesleyan.edu (D.K.); kthayer{at}wesleyan.edu (K.S.)
