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bioRxiv · 10.1101/2022.05.18.492265

Phenol Sensing in Nature Modulated via a Conformational Switch Governed by Dynamic Allostery

Singh, J.·Sahil, M.·Ray, S.·Dcosta, C.·Panjikar, S.·Krishnamoorthy, G.·Mondal, J.·Anand, R.
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Abstract

NtrC family of proteins sense external stimuli and accordingly stimulate stress and virulence pathways via activation of associated {sigma}54-dependent RNA polymerases. Here, we establish that MopR, an NtrC protein, harbors a dynamic bi-directional electrostatic network that connects the phenol pocket to two distal regions, namely the "G-hinge" and the "allo-steric-linker". While G-hinge influences the entry of phenol, the allosteric-linker passes the signal to the downstream ATPase domain. Phenol binding induces a rewiring of the electrostatic connections by eliciting dynamic allostery, and it was demonstrated that perturbation of the core relay residues results in a complete loss of ATPase stimulation. A mutation of the G-hinge,[~]20[A] from the phenol pocket, demonstrated altered flexibility by shifting the pattern of conformational states accessed, leading to a protein with 7-fold enhanced phenol binding ability and enhanced transcriptional activation. A global analysis illustrates that dynamic allostery-driven conserved community networks are universal and evolutionarily conserved across species.

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Singh, J., Sahil, M., Ray, S., Dcosta, C., Panjikar, S., Krishnamoorthy, G., Mondal, J., Anand, R.. 2022-05-18. Phenol Sensing in Nature Modulated via a Conformational Switch Governed by Dynamic Allostery. https://doi.org/10.1101/2022.05.18.492265

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