Histidine kinase regulation by a cyclophilin-like inhibitor

Jacques, David A., Langley, David B. B., Jeffries, Cy M., Cunningham, Katherine A., Burkholder, William F., Guss, J. Mitchell and Trewhella, Jill (2008) Histidine kinase regulation by a cyclophilin-like inhibitor. Journal of Molecular Biology, 384 2: 422-435. doi:10.1016/j.jmb.2008.09.017

Author Jacques, David A.
Langley, David B. B.
Jeffries, Cy M.
Cunningham, Katherine A.
Burkholder, William F.
Guss, J. Mitchell
Trewhella, Jill
Title Histidine kinase regulation by a cyclophilin-like inhibitor
Journal name Journal of Molecular Biology   Check publisher's open access policy
ISSN 0022-2836
Publication date 2008-12-12
Sub-type Article (original research)
DOI 10.1016/j.jmb.2008.09.017
Volume 384
Issue 2
Start page 422
End page 435
Total pages 14
Place of publication London, United Kingdom
Publisher Academic Press
Language eng
Formatted abstract
The sensor histidine kinase A (KinA) from Bacillus subtilis triggers a phosphorelay that activates sporulation. The antikinase KipI prevents sporulation by binding KinA and inhibiting the autophosphorylation reaction. Using neutron contrast variation, mutagenesis, and fluorescence data, we show that two KipI monomers bind via their C-domains at a conserved proline in the KinA dimerization and histidine-phosphotransfer (DHp) domain. Our crystal structure of the KipI C-domain reveals the binding motif has a distinctive hydrophobic groove formed by a five-stranded antiparallel β-sheet; a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis–trans peptidyl-prolyl isomerases. We propose that the DHp domain of KinA transmits conformational signals to regulate kinase activity via this proline-mediated interaction. Given that both KinA and KipI homologues are widespread in the bacterial kingdom, this mechanism has broad significance in bacterial signal transduction.
Keyword Bacterial signal transduction
Histidine kinase inhibition
Small-angle scattering
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 25 Jul 2012, 10:58:05 EST by Susan Allen on behalf of Institute for Molecular Bioscience