Synonymous codon usage influences the local protein structure observed

Abstract

Translation of mRNA into protein is a unidirectional information flow process. Analysing the input (mRNA) and output (protein) of translation, we find that local protein structure information is encoded in the mRNA nucleotide sequence. The Coding Sequence and Structure (CSandS) database developed in this work provides a detailed mapping between over 4000 solved protein structures and their mRNA. CSandS facilitates a comprehensive analysis of codon usage over many organisms. In assigning translation speed, we find that relative codon usage is less informative than tRNA concentration. For all speed measures, no evidence was found that domain boundaries are enriched with slow codons. In fact, genes seemingly avoid slow codons around structurally defined domain boundaries. Translation speed, however, does decrease at the transition into secondary structure. Codons are identified that have structural preferences significantly different from the amino acid they encode. However, each organism has its own set of 'significant codons'. Our results support the premise that codons encode more information than merely amino acids and give insight into the role of translation in protein folding.

Figure 1.

Examples of codons that are over-represented at the start of helices compared to other codons in their synonymous codon family. In each case the codon of interest is displayed in red and all synonymous codons are shown in blue. Significant codon positioning is highlighted using ball and stick representation. The Glu codon GAA is over-represented at the start of helices in Ecoli (A) and in Human the Ser codon TCA is over-represented at H1 (B). PDB structures 2GFF (A) and 1L9L (B) are used to illustrate the examples. Image created using Chimera (50).

Figure 2.

Domain boundaries are deficient in slow codons and enriched in fast codons. Data is shown using translation speed calculated from tRNA concentration (A) and the original CAI (B). Solid lines represent fast codons and dotted lines slow codons. Enrichment (Y-axis), the percentage increase over that found in the protein as a whole, is shown for different length sections (X-axis) centred on the domain boundary. For tRNA concentration (A) only Ecoli data is available, with data displayed for all three codon speed windows considered in this study (3, 9 and 19). In (B) data is displayed for Ecoli (black) and Yeast (grey) using a codon speed window of 19.

Figure 3.

Change in relative translation speed (Y-axis) on the transition between secondary structures (X-axis). In moving from coil into helix (A) or coil into strand (B) a clear decrease in translation speed is observed. The transition from helix into coil (C) or strand into coil (D) is also characterized by a decrease in translation speed. In this instance, around three residues downstream of (N-terminal to) the transition site. This is followed by an increase in translation speed as the coil region is produced. Data shown for Ecoli using a speed window of three codons.