Insights Into the Conformational Dynamics of the Cytoplasmic Domain of Metal‐Sensing Sensor Histidine Kinase ZraS

• DOI: 10.1002/prot.26819
• Publication Date: 2025-03-12T01:02:33Z
• Authors: Nilima Mahapatra; Pranjal Mahanta; Shubhant Pandey; Rudresh Acharya
• Keywords: Histidine kinase; Linker; Protein kinase domain; Random hexamer; Helix (gastropod); Salt bridge

ZraS is a metal sensor integral to ZraPSR, two-component signaling system found in enterobacters. It belongs family of bifunctional histidine kinases (SHKs) and speculated sense zinc-induced stress on the bacterial envelope. Information structure-function relationship elusive due lack full-length structures, intrinsically dynamic behavior, difficulty trapping them active state conformations. While kinase domains (KDs) few SHKs are well characterized, they exhibit significant functional diversity attributed their modular multi-domain arrangement cytoplasmic region, combined with other signal transducing elements such as simple helices, HAMP, PAS domains. We report crystal structure entire region Escherichia coli (EcZraS-CD) resolved at resolution 2.49 Å, comprising unique helical linker KD. In asymmetric unit, four molecules assemble homodimers trapped two ligand-bound occluded conformers. Our analysis using these conformers shows that modulation dimer bundle through segmental bending, sliding, rotation leads reorganization dimerization interface during activation. Further, our reveals significance aromatic amino acid interactions loop residues base regulating directionality autophosphorylation. also performed an vitro coupled assay determine ATPase activity. Overall, findings provide structure-based mechanistic insights into process autophosphorylation trans-acting SHKs.