The structural basis for signal promiscuity in a bacterial chemoreceptor

Area of Science:

• Structural biology
• Biochemistry
• Microbiology

Background:

• Chemosensory pathways initiate signaling via ligand binding to chemoreceptor ligand-binding domains (LBDs).
• The PcaY_PP chemoreceptor exhibits a broad signal range, recognizing molecules with a C6-ring and carboxyl group.
• Previous studies indicated some PcaY_PP signals lack apparent metabolic value.

Purpose of the Study:

• To elucidate the high-resolution structures of the PcaY_PP-LBD.
• To investigate the structural basis of ligand binding and signaling mechanisms.
• To compare PcaY_PP-LBD with other chemoreceptor domains.

Main Methods:

• High-resolution crystallography of PcaY_PP-LBD in apo and holo states.
• Microcalorimetric titration of site-directed mutants.
• Structural comparisons with Tar and Tsr chemoreceptors.

Main Results:

• Determined structures of PcaY_PP-LBD with and without ligands (glycerol, protocatechuate, quinate, benzoate, salicylate).
• Identified key residues (arginine, polar residues) involved in extensive hydrogen bonding networks with ligands.
• Observed rigid-body scissoring movements upon ligand binding, not piston-like helix shifts.
• Revealed significant structural differences and a distinct ligand-binding site compared to Tar and Tsr receptors.

Conclusions:

• PcaY_PP-LBD exhibits unique structural features and ligand-binding mechanisms.
• Ligand binding induces conformational changes involving scissoring movements of the dimer.
• Demonstrated significant structural and functional diversity among four-helix bundle (4HB) domains in chemoreceptors.