Diversity of function and higher-order structure within HWE sensor histidine kinases

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Protein oligomeric state is crucial for structure and function, typically conserved evolutionarily.
• Histidine kinases (HKs) are prokaryotic environmental sensors, usually functioning as transmembrane homodimers.
• Exceptions exist, like hemoglobins, demonstrating evolutionary adaptation of oligomerization for novel regulation.

Purpose of the Study:

• To investigate the diversity of oligomerization states and regulatory mechanisms in the HWE/HisKA2 family of histidine kinases.
• To explore how evolutionary changes in oligomerization impact HK function.
• To identify potential novel regulatory modes in environmental sensor proteins.

Main Methods:

• Biophysical and biochemical characterization of monomeric and dimeric histidine kinase homologs.
• Analysis of light-oxygen-voltage (LOV) and Per-ARNT-Sim (PAS) domain-containing HKs.
• Examination of protein-protein interaction interfaces involved in dimerization.

Main Results:

• Identified a monomeric soluble HWE/HisKA2 HK (EL346, a photosensing LOV-HK).
• Characterized multiple EL346 homologs exhibiting diverse oligomeric states (dimeric, monomer-dimer interconversion) and light-dependent functions.
• Found that dimerization status influences enzymatic activity in some Per-ARNT-Sim-HKs and identified multiple dimerization interfaces in a dimeric LOV-HK.

Conclusions:

• The HWE/HisKA2 family displays significant diversity in oligomeric states and regulatory strategies.
• Oligomerization state is a flexible evolutionary trait in histidine kinases, enabling novel regulatory mechanisms.
• Findings suggest potential for new regulatory modes and oligomeric states in this important class of environmental sensors.