Atomic coordinates and structure factors for the DNA-binding domain of Cupriavidus necatorNH9 CbnR in complex with RBS are available in the Protein Data Bank under the accession code 5XXP.

LysR‐type transcription regulators (LTTRs) comprise one of the largest families of transcriptional regulators in bacteria. They are typically homo‐tetrameric proteins and interact with promoter DNA of ~ 50–60 bp. Earlier biochemical studies have suggested that LTTR binding to promoter DNA bends the DNA and, upon inducer binding, the bend angle of the DNA is reduced through a quaternary structure change of the tetrameric LTTR, leading to the activation of transcription. To date, crystal structures of full‐length LTTRs, DNA‐binding domains (DBD) with their target DNAs, and the regulatory domains with and without inducer molecules have been reported. However, these crystal structures have not provided direct evidence of the quaternary structure changes of LTTRs or of the molecular mechanism underlying these changes. Here, we report the first crystal structure of a full‐length LTTR, CbnR, in complex with its promoter DNA. The crystal structure showed that, in the absence of bound inducer molecules, the four DBDs of the tetrameric CbnR interact with the promoter DNA, bending the DNA by ~ 70°. Structural comparison between the DNA‐free and DNA‐bound forms demonstrates that the quaternary structure change of the tetrameric CbnR required for promoter region‐binding arises from relative orientation changes of the three domains in each subunit. The mechanism of the quaternary structure change caused by inducer binding is also discussed based on the present crystal structure, affinity analysis between CbnR and the promoter DNA, and earlier mutational studies on CbnR. Database Atomic coordinates and structure factors for the full‐length Cupriavidus necator NH9 CbnR in complex with promoter DNA are available in the Protein Data Bank under the accession code https://doi.org/10.2210/pdb7D98/pdb.

LysR-type transcriptional regulators (LTTRs) comprise one of the largest families of transcriptional regulators in bacteria andcontrol gene expression of various types of metabolic, virulence and physiological functions. LTTRs typically form homotetramers and require an inducer molecule(s) to activate the transcription of target genes. The N-terminal region of LTTRs contains a DNAbinding domain (DBD) with the winged helix-turn-helix motif that specifically binds the promoter region of target genes. The C-terminal region of LTTRs is connected to the DBD by a linker helix and forms the regulatory domain (RD) that contains a binding pocket for inducer molecules. Crystal structures of several LTTR family members together with their biochemical analyses have provided a potential mechanism for the initial process of transcriptional activation by LTTRs. First, helix 3 of the winged helix-turn-helix motif in DBD is supposed to distinguish the recognition binding site (RBS) in the promoter region, resulting in complex formation through interactions between two DBDs in the tetrameric LTTR and RBS. Formation of this complex seems to enable interactions between the other two DBDs in the LTTR tetramer and the activation binding site (ABS) in the promoter region.The binding of the tetrameric LTTR to both the RBS and ABS causes the promoter DNA to adopt a bent structure because the four DBDs in the tetrameric LTTR are arranged in a V-shaped manner at the bottom of the LTTR. Interaction of an inducer molecule(s) with the RD seems to cause a quaternary structural change of the LTTR that relaxes the bending angle of the promoter DNA with a concomitant shift of the bound DBDs at the ABS. These events facilitate recruitment of RNA polymerase to its binding site in the promoter region, which overlaps with the ABS for LTTR.

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