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J Mol Biol. 2008 Dec 12;384(2):422-35. doi: 10.1016/j.jmb.2008.09.017. Epub 2008 Sep 16.

Histidine kinase regulation by a cyclophilin-like inhibitor.

Author information

1
School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New South Wales 2006, Australia.

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 beta-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.

PMID:
18823995
DOI:
10.1016/j.jmb.2008.09.017
[Indexed for MEDLINE]

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