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

Kate J. Newberry, Shunji Nakano, Peter Zuber, Richard G. Brennan

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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 σA. 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.

Original languageEnglish (US)
Pages (from-to)15839-15844
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number44
DOIs
StatePublished - Nov 1 2005

Fingerprint

DNA-Directed RNA Polymerases
Bacillus subtilis
Disulfides
Nucleic Acid Conformation
Protein Subunits
Oxidation-Reduction
Binding Sites
Gene Expression

Keywords

  • ArsC family
  • Global transcription regulation
  • Oxidative/disulfide stress

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{fa1b201e9cf14aa28f976dcc84156a44,
title = "Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional regulator, Spx, in complex with the α C-terminal domain of RNA polymerase",
abstract = "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 σA. 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.",
keywords = "ArsC family, Global transcription regulation, Oxidative/disulfide stress",
author = "Newberry, {Kate J.} and Shunji Nakano and Peter Zuber and Brennan, {Richard G.}",
year = "2005",
month = "11",
day = "1",
doi = "10.1073/pnas.0506592102",
language = "English (US)",
volume = "102",
pages = "15839--15844",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "44",

}

TY - JOUR

T1 - Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional regulator, Spx, in complex with the α C-terminal domain of RNA polymerase

AU - Newberry, Kate J.

AU - Nakano, Shunji

AU - Zuber, Peter

AU - Brennan, Richard G.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - 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 σA. 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.

AB - 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 σA. 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.

KW - ArsC family

KW - Global transcription regulation

KW - Oxidative/disulfide stress

UR - http://www.scopus.com/inward/record.url?scp=27644512305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644512305&partnerID=8YFLogxK

U2 - 10.1073/pnas.0506592102

DO - 10.1073/pnas.0506592102

M3 - Article

C2 - 16249335

AN - SCOPUS:27644512305

VL - 102

SP - 15839

EP - 15844

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 44

ER -