The induction mechanism of the flavonoid-responsive regulator FrrA

January 5, 2022

Title

The induction mechanism of the flavonoid-responsive regulator FrrA

Author

Nadine Werner, Sebastiaan Werten, Jens Hoppend, Gottfried J. Palm, Michael Gottfert, Winfried Hinrichs

Year

2021

Journal

FEBS Journal

Abstract

Bradyrhizobium diazoefficiens, a bacterial symbiont of soybean and other leguminous plants, enters a nodulation-promoting genetic programme in the presence of host-produced flavonoids and related signalling compounds. Here, we describe the crystal structure of an isoflavonoid-responsive regulator (FrrA) from Bradyrhizobium, as well as cocrystal structures with inducing and noninducing ligands (genistein and naringenin, respectively). The structures reveal a TetR-like fold whose DNA-binding domain is capable of adopting a range of orientations. A single molecule of either genistein or naringenin is asymmetrically bound in a central cavity of the FrrA homodimer, mainly via C–H contacts to the π-system of the ligands. Strikingly, however, the interaction does not provoke any conformational changes in the repressor. Both the flexible positioning of the DNA-binding domain and the absence of structural change upon ligand binding are corroborated by small-angle X-ray scattering (SAXS) experiments in solution. Together with a model of the promoter-bound state of FrrA our results suggest that inducers act as a wedge, preventing the DNA-binding domains from moving close enough together to interact with successive positions of the major groove of the palindromic operator.

Instrument

J-810

Keywords

Bradyrhizobium, structure, DNA-binding