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The induction mechanism of the flavonoid‐responsive regulator FrrA
Author(s) -
Werner Nadine,
Werten Sebastiaan,
Hoppen Jens,
Palm Gottfried J.,
Göttfert Michael,
Hinrichs Winfried
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.16141
Subject(s) - repressor , tetr , regulator , naringenin , cooperativity , eriodictyol , stereochemistry , chemistry , dna , biophysics , biology , biochemistry , transcription factor , flavonoid , gene , antioxidant
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.