The ability of group A Streptococcus (GAS) to survive and replicate intracellularly for deep tissue infection requires the coordination of gene expression that relies on the activity of transcriptional factors in a regulatory network. NAD-glycohydrolase (NADase; Nga) has been identified to involve in GAS replication inside endothelial cells . Expression of Nga is transcriptionally repressed by regulator Rgg , however, the molecular details remain unclear. Our study demonstrated that Rgg acts as a negative regulator of NADase. In addition, we applied small-angle X-ray scattering to construct the full atomic model of Rgg, including the DNA-binding helix-turn-helix motif of Rgg which is not visible in the currently available homologous structures . Furthermore, we identified the key residues of Rgg involved in regulating the NADase activity by structure-based mutagenesis studies. Our results provide the structural information of Rgg to understand the mode of action of Rgg associated with GAS replication in endothelium.
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