Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional regulator, Spx, in complex with the α C-terminal domain of RNA polymerase

Spx, a global transcription regulator in Bacillus subtilis, interacts with the C-terminal domain of the alpha subunit (alpha CTD) of RNA polymerase to control gene expression under conditions of disulfide stress, which is sensed by disulfide bond formation between Spx residues C10 and C13. Here, we describe the crystal structure of the B. subtilis alpha CTD bound to oxidized Spx. Analysis of the complex reveals interactions between three regions of "anti-alpha" Spx and helix alpha 1 and the "261" determinant of alpha CTD. The former contact could disrupt the interaction between alpha CTD and activator proteins or alter the DNA-bound conformation of alpha CTD, thereby repressing activator-stimulated transcription. Binding to the 261 determinant would prevent interaction between alpha CTD and region 4 of sigma(A). Intriguingly, the Spx disulfide bond is far from the alpha CTD-Spx interface, suggesting that Spx regulates transcription allosterically or through the redox-dependent creation or destruction of binding sites for additional components of the transcription machinery.