Atomic insights into the signaling landscape of E. coli PhoQ histidine kinase from molecular dynamics simulations.

ABSTRACT: Bacteria rely on two-component systems to sense environmental cues and regulate gene expression for adaptation. The PhoQ/PhoP system exemplifies this crucial role, playing a key part in sensing magnesium (Mg²⁺) levels, antimicrobial peptides, mild acidic pH, osmotic upshift, and long-chain unsaturated fatty acids, promoting virulence in certain bacterial species. However, the precise details of PhoQ activation remain elusive. To elucidate PhoQ's signaling mechanism at atomic resolution, we combined AlphaFold2 predictions with molecular modeling and carried out extensive Molecular Dynamics (MD) simulations. Our MD simulations revealed three distinct PhoQ conformations that were validated by experimental data. Notably, one conformation was characterized by Mg²⁺ bridging

SUBMITTER: Lazaridi S 

PROVIDER: S-EPMC11291726 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature