The primary function of the CheY protein is to regulate flagellar motility in motile bacteria such as Escherichia coli and Thermotoga maritima. Although the general determinants of thermal stability in CheY from the hyperthermophilic bacterium T. maritima (TmY) have been proposed, the molecular mechanisms that enable this protein to remain structurally and functionally competent at elevated temperatures are not fully understood. Here, we investigated the thermal stability of TmY through all-atom molecular dynamics simulations, using three independent trajectories of 1 μs each at five different temperatures. Equivalent simulations were performed for its mesophilic homologue from E. coli (EcY) to enable a direct comparison under identical conditions. Our observations show that TmY preserves its native fold and global compactness across the entire temperature range, whereas EcY exhibits progressive destabilization and unfolds at high temperatures. Mechanistically, the enhanced thermal resistance of TmY is associated with an extensive network of salt bridges that interconnect secondary-structure elements and couple the N- and C-terminal domains. These electrostatic networks act as stabilizing scaffolds that restrain local flexibility, preserve domain communication, and maintain a tightly packed globular architecture under thermal stress, providing a molecular basis for the superior stability of TmY relative to its mesophilic counterpart.
Alas et al. (Tue,) studied this question.