title: Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional regulator, Spx, in complex with the alpha C-terminal domain of RNA polymerase.
abstract: Spx, a global transcription regulator in Bacillus subtilis, interacts with the C-terminal domain of the alpha subunit (alphaCTD) 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 alphaCTD bound to oxidized Spx. Analysis of the complex reveals interactions between three regions of "anti-alpha" Spx and helix alpha1 and the "261" determinant of alphaCTD. The former contact could disrupt the interaction between alphaCTD and activator proteins or alter the DNA-bound conformation of alphaCTD, thereby repressing activator-stimulated transcription. Binding to the 261 determinant would prevent interaction between alphaCTD and region 4 of sigma(A). Intriguingly, the Spx disulfide bond is far from the alphaCTD-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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Newberry
authors.forename: Shunji
authors.initials: S
authors.lastname: Nakano
authors.forename: Peter
authors.initials: P
authors.lastname: Zuber
authors.forename: Richard G
authors.initials: RG
authors.lastname: Brennan
mesh_terms: D001412:Bacillus subtilis / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D003460:Crystallization; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D010084:Oxidation-Reduction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D012321:DNA-Directed RNA Polymerases; C113275:RNA polymerase alpha subunit