Structure and mechanism of action of Sda, an inhibitor of the histidine kinases that regulate initiation of sporulation in Bacillus subtilis

Rowland, S. L., Burkholder, W. F., Cunningham, K. A., Maciejewski, M. W., Grossman, A. D. and King, G. F. (2004) Structure and mechanism of action of Sda, an inhibitor of the histidine kinases that regulate initiation of sporulation in Bacillus subtilis. Molecular Cell, 13 5: 689-701. doi:10.1016/S1097-2765(04)00084-X


Author Rowland, S. L.
Burkholder, W. F.
Cunningham, K. A.
Maciejewski, M. W.
Grossman, A. D.
King, G. F.
Title Structure and mechanism of action of Sda, an inhibitor of the histidine kinases that regulate initiation of sporulation in Bacillus subtilis
Journal name Molecular Cell   Check publisher's open access policy
ISSN 1097-2765
Publication date 2004
Sub-type Article (original research)
DOI 10.1016/S1097-2765(04)00084-X
Volume 13
Issue 5
Start page 689
End page 701
Total pages 13
Place of publication Cambridge
Publisher Cell Press
Language eng
Subject 0601 Biochemistry and Cell Biology
1108 Medical Microbiology
Abstract Histidine kinases are used extensively in prokaryotes to monitor and respond to changes in cellular and environmental conditions. In Bacillus subtilis, sporulation-specific gene expression is controlled by a histidine kinase phosphorelay that culminates in phosphorylation of the SpoOA transcription factor. Sda provides a developmental checkpoint by inhibiting this phosphorelay in response to DNA damage and replication defects. We show that Sda acts at the first step in the relay by inhibiting autophosphorylation of the histidine kinase KinA. The structure of Sda, which we determined using NMR, comprises a helical hairpin. A cluster of conserved residues on one face of the hairpin mediates an interaction between Sda and the KinA dimerization/phosphotransfer domain. This interaction stabilizes the KinA dimer, and the two proteins form a stable heterotetramer. The data indicate that Sda forms a molecular barricade that inhibits productive interaction between the catalytic and phosphotransfer domains of KinA.
Keyword Biochemistry & Molecular Biology
Cell Biology
2-component Signal-transduction
Escherichia-coli Osmosensor
Phosphorelay Proteins
Molecular Recognition
Nmr Structure
Domain
Autophosphorylation
Envz
Sequence
Meliloti
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 19 Sep 2007, 19:13:59 EST