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 [1]. Expression of Nga is transcriptionally repressed by regulator Rgg [2], 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 [3]. 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.
References
[1] Bastiat-Sempe B et al, mBio 5 (2014) e01690.
[2] Dmitriev AV et al, J Bacteriol 188 (2006) 7230.
[3] Parashar Vet al, Proc. Natl. Acad. Sci. 112 (2015) 5177.