King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia
Vladlena Kharchenko
King Abdullah University of Science and Technology (KAUST), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia
Chenyi Liao
Department of Chemistry, The University of Vermont, Burlington, United States
Franceline Huser
King Abdullah University of Science and Technology (KAUST), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia
Jacob M Remington
King Abdullah University of Science and Technology (KAUST), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia
Anand K Radhakrishnan
King Abdullah University of Science and Technology (KAUST), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia
Mariusz Jaremko
King Abdullah University of Science and Technology (KAUST), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia
King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal, Saudi Arabia; Centre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, Montpellier, France
The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less nuclear magnetic resonance spectroscopy, and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the exact modus operandi for H-NS-mediated environmental sensing and suggested that this sensing mechanism resulted from the exaptation of an ancestral protein feature.