Changes in the osmolarity of the environment pose a great threat to bacteria, which need to adequately and timely respond to this stress. In Firmicutes, the bacterial nucleotide second messenger cyclic di-AMP takes up a pivotal role in this response by up- and down regulating expression of potassium and osmolyte transporters or adjusting their activity. Among these is the glycine-betaine transporter BusA. Its transcription is under control of the c-di-AMP responsive transcriptional repressor BusR. The molecular details of this pathway have so far been elusive. Now, using a hybrid method approach of X-ray crystallography and cryo-electron microscopy, Gregor Witte and his team obtained structures of Streptococcus agalactiae BusR in various states. These structures unravel how c-di-AMP allosterically dissolves an autoinhibited state and allows BusR to bind to its target DNA. Thereby, the intriguing molecular architecture of BusR acts as molecular ruler to guide proper binding site recognition. The new findings are published in Nucleic Acids Research (Bandera et al., 2021).
BusR senses bipartite DNA binding motifs by a unique molecular ruler architecture.
Bandera AM, Bartho J, Lammens K, Drexler DJ, Kleinschwärzer J, Hopfner KP, Witte G.
Nucleic Acids Res. 2021 Aug 25:gkab736.