Delineating PAS-HAMP interaction surfaces and signalling-associated changes in the aerotaxis receptor Aer

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• The Escherichia coli aerotaxis receptor, Aer, senses oxygen and redox potential using a PAS domain with bound FAD.
• Signal transduction in most chemoreceptors involves a linear pathway from sensor to HAMP domain.

Purpose of the Study:

• To elucidate the mechanism by which the Aer PAS domain controls aerotaxis through interactions with the HAMP domain.
• To investigate the conformational changes in Aer domains during signal transduction.

Main Methods:

• Utilized cysteine substitutions and solvent accessibility probing to map interaction surfaces between Aer PAS, HAMP, and proximal signaling domains.
• Analyzed domain interactions in both kinase-off and kinase-on states.

Main Results:

• Identified direct, lateral interactions between the Aer PAS and HAMP domains, distinct from canonical signaling.
• Mapped interaction surfaces and proposed a refined Aer PAS-HAMP interaction model.
• Observed altered domain accessibility correlating with kinase activity, supporting an alternating static-dynamic model.

Conclusions:

• Aer-PAS controls aerotaxis via direct PAS-HAMP lateral interactions, not solely through backbone propagation.
• An alternating static-dynamic model explains signal transduction: oxidized Aer-PAS induces a static HAMP and dynamic proximal domain (kinase-off), while reduced Aer-PAS leads to a dynamic HAMP and static proximal domain (kinase-on).