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Annual Review of Biophysics

Volume 53, 2024

The Effects of Codon Usage on Protein Structure and Folding

Abstract

The rate of protein synthesis is slower than many folding reactions and varies depending on the synonymous codons encoding the protein sequence. Synonymous codon substitutions thus have the potential to regulate cotranslational protein folding mechanisms, and a growing number of proteins have been identified with folding mechanisms sensitive to codon usage. Typically, these proteins have complex folding pathways and kinetically stable native structures. Kinetically stable proteins may fold only once over their lifetime, and thus, codon-mediated regulation of the pioneer round of protein folding can have a lasting impact. Supporting an important role for codon usage in folding, conserved patterns of codon usage appear in homologous gene families, hinting at selection. Despite these exciting developments, there remains few experimental methods capable of quantifying translation elongation rates and cotranslational folding mechanisms in the cell, which challenges the development of a predictive understanding of how biology uses codons to regulate protein folding.

Keyword(s): cotranslational protein folding, functional protein production, gene expression, rare codons, synonymous codon substitution, translation elongation
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2024-07-16
2024-10-10
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/content/journals/10.1146/annurev-biophys-030722-020555
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The Effects of Codon Usage on Protein Structure and Folding
Annual Review of Biophysics 53, 87 (2024); https://doi.org/10.1146/annurev-biophys-030722-020555
/content/journals/10.1146/annurev-biophys-030722-020555
/content/journals/10.1146/annurev-biophys-030722-020555
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