Synonymous coding significantly affects the domain swapping propensity of myoglobin

Co-translational folding is a critical, yet poorly understood, aspect of protein biogenesis due to its transient, heterogeneous, and experimentally inaccessible nature. Using a myoglobin variant engineered towards increased domain swapping, we show that stable dimers formed during heterologous E. Coli expression revert to the monomeric state following denaturation - renaturation and that domain swapping propensity is significantly affected by synonymous coding. Wider implications for the role of synonymous coding in aggregation and disease are discussed.