Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Bacteria utilize two-component systems, comprising sensor histidine kinases (HK) and response regulators (RR), for environmental sensing.
• Signal transduction involves conserved protein domains mediating autokinase, phosphotransfer, and phosphatase activities, regulating RR phosphorylation levels.

Purpose of the Study:

• To elucidate the structural basis of partner specificity and signal transduction in bacterial two-component systems.
• To determine the structure of the Thermotoga maritima HK853-RR468 complex and its components.

Main Methods:

• X-ray crystallography was employed to determine the structures of HK853-RR468 complex, free RR468, and BeF(3)-bound RR468.
• Biochemical assays were performed to analyze the autokinase and phosphatase activities.

Main Results:

• The study reports the structures of the entire cytoplasmic portion of HK853 complexed with RR468, and isolated RR468.
• Structural and biochemical data provide insights into partner recognition, phosphorylation state recognition, and the phosphatase catalytic mechanism.
• HK853 autokinase activity occurs via a cis autophosphorylation mechanism.

Conclusions:

• The findings offer a detailed model for signal transduction in bacterial two-component systems.
• Understanding these mechanisms is crucial for deciphering bacterial environmental responses and developing targeted interventions.