Comparative Molecular Dynamics Study of the Thermal Stability of CheY Proteins from Hyperthermophilic and Mesophilic Organisms

TL;DR

This study compares the thermal stability of CheY proteins from a heat-loving and a normal-temperature bacterium using molecular simulations.

Contribution

The paper reveals how salt bridges stabilize the CheY protein from a hyperthermophilic organism under high temperatures.

Findings

TmY maintains its structure at high temperatures, unlike EcY which unfolds.

Salt bridges in TmY connect secondary structures and stabilize the protein.

These electrostatic networks preserve domain communication and compactness under thermal stress.

Abstract

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.

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