Role for gene sequence, codon bias and mRNA folding energy in modulating structural symmetry of proteins

Structural symmetry in proteins is commonly observed in the majority of fundamental protein folds. Meanwhile, nascent polypeptide chains of proteins have the potential to start the co-translational folding process and this process can have drastic effects on protein structure. Thus we are interested in understanding mechanisms that gene adopts in specifying structural symmetry in proteins. In the present paper, we reveal that for two representative symmetric proteins from (αβ)₈-barrel fold and beta-trefoil fold, intragenic symmetry is detected in the corresponding gene sequences. Codon bias and mRNA folding energy might be involved in mediating translation speed for the formation of structural symmetry: at least one major decrease in both codon bias and mRNA folding energy can be observed in the connecting region of the symmetric substructures along the codon sequence. Results suggest that gene duplication and fusion is responsible for structural symmetry in these proteins, and the usage of rare codons or higher order of secondary structure near the boundaries of symmetric substructures might be selected in order to slow down translation speed for effectively co-translational folding process of symmetric proteins.