Cooperative ligand binding in a bacterial heme-based oxygen sensor.

Area of Science:

• Microbiology
• Biochemistry
• Structural Biology

Background:

• Bacteria sense environmental signals like molecular oxygen (O2) to regulate phenotypes.
• Globin-coupled sensors (GCS) are heme proteins involved in O2-dependent regulation of bacterial virulence, motility, and biofilm formation.
• Cooperative ligand binding, common in mammalian hemoglobins, was previously unobserved in bacterial sensor globins.

Purpose of the Study:

• To investigate O2-dependent allosteric communication within the globin domains of the Pectobacterium carotovorum GCS (PccGCS).
• To determine if cooperative ligand binding occurs in bacterial sensor globins.

Main Methods:

• Equilibrium O2-binding measurements
• X-ray crystallography
• Resonance Raman spectroscopy
• Hydrogen-deuterium exchange mass spectrometry

Main Results:

• Demonstrated O2-dependent allosteric communication between globin domains in PccGCS.
• Proposed a model for allosteric regulation involving distal heme pocket conformational changes and dimer interface helix dynamics.
• Identified cooperative ligand binding in a bacterial heme protein family for the first time.

Conclusions:

• Cooperative O2 binding in PccGCS allows for robust bacterial responses to subtle changes in oxygen levels.
• Heme pocket residues are crucial for transducing O2 binding signals within the dimer.
• This work suggests a pathway for signal transduction in dimeric myoglobin-like sensor proteins.