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 α subunit (αCTD) 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 αCTD bound to oxidized Spx. Analysis of the complex reveals interactions between three regions of "anti-alpha" Spx and helix α1 and the "261" determinant of αCTD. The former contact could disrupt the interaction between αCTD and activator proteins or alter the DNA-bound conformation of αCTD, thereby repressing activator-stimulated transcription. Binding to the 261 determinant would prevent interaction between αCTD and region 4 of σ^A. Intriguingly, the Spx disulfide bond is far from the αCTD-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.