A mechanism of modulating the direction of flagellar rotation in bacteria by fumarate and fumarate reductase.

08:00 EDT 11th August 2019 | BioPortfolio

Summary of "A mechanism of modulating the direction of flagellar rotation in bacteria by fumarate and fumarate reductase."

Fumarate, an electron acceptor in anaerobic respiration of Escherichia coli, has an additional function of assisting the flagellar motor to shift from counterclockwise to clockwise rotation, with a consequent modulation of the bacterial swimming behavior. Fumarate transmits its effect to the motor via the fumarate reductase complex (FrdABCD), shown to bind to FliG - one of the motor's switch proteins. How binding of the FrdABCD respiratory enzyme to FliG enhances clockwise rotation and how fumarate is involved in this activity, have remained puzzling. Here we show that the FrdA subunit in the presence of fumarate is sufficient for binding to FliG and for clockwise enhancement. We further demonstrate by in vitro binding assays and super-resolution microscopy in vivo that the mechanism by which fumarate-occupied FrdA enhances clockwise rotation involves its preferential binding to the clockwise state of FliG (FliG). Continuum electrostatics combined with docking analysis and conformational sampling endorsed the experimental conclusions and suggested that the FrdA-FliG interaction is driven by the positive electrostatic potential generated by FrdA and the negatively charged areas of FliG. They further demonstrated that fumarate changes FrdA's conformation to one that can bind to FliG. These findings also show that the reason for the failure of the succinate dehydrogenase flavoprotein SdhA (an almost-identical analog of FrdA shown to bind to FliG equally well) to enhance clockwise rotation is that it has no binding preference for FliG. We suggest that this mechanism is physiologically important as it can modulate the magnitude of ΔG between the clockwise and counterclockwise states of the motor to tune the motor to the growth conditions of the bacteria.


Journal Details

This article was published in the following journal.

Name: Journal of molecular biology
ISSN: 1089-8638


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