The Structure of the KinA-Sda Complex Suggests an Allosteric Mechanism of Histidine Kinase Inhibition

The Bacillus subtilis histidine kinase KinA controls activation of the transcription factor governing sporulation, Spo0A. The decision to sporulate involves KinA phosphorylating itself on a conserved histidine residue, after which the phosphate moiety is relayed via two other proteins to Spo0A. The...

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Bibliographic Details
Published in:Journal of molecular biology 2007-04, Vol.368 (2), p.407-420
Main Authors: Whitten, Andrew E., Jacques, David A., Hammouda, Boualem, Hanley, Tracey, King, Glenn F., Guss, J. Mitchell, Trewhella, Jill, Langley, David B.
Format: Article
Language:English
Subjects:
Allosteric Regulation
Amino Acid Sequence
BACILLUS SUBTILIS
Bacillus subtilis - enzymology
Bacterial Proteins - antagonists & inhibitors
Bacterial Proteins - chemistry
BASIC BIOLOGICAL SCIENCES
DIMERIZATION
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
HISTIDINE
Histidine Kinase
KinA
Models, Molecular
Molecular Sequence Data
neutron contrast variation
NEUTRONS
Other,OTHER
PHOSPHATES
PHYSICS OF ELEMENTARY PARTICLES AND FIELDS
Protein Binding
Protein Kinases - chemistry
Protein Structure, Secondary
Protein Structure, Tertiary
PROTEINS
SCATTERING
Scattering, Radiation
Sda
small-angle scattering
Solutions
Structure-Activity Relationship
TARGETS
TRANSCRIPTION FACTORS
X-Ray Diffraction
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Summary:The Bacillus subtilis histidine kinase KinA controls activation of the transcription factor governing sporulation, Spo0A. The decision to sporulate involves KinA phosphorylating itself on a conserved histidine residue, after which the phosphate moiety is relayed via two other proteins to Spo0A. The DNA-damage checkpoint inhibitor Sda halts this pathway by binding KinA and blocking the autokinase reaction. We have performed small-angle X-ray scattering and neutron contrast variation studies on the complex formed by KinA and Sda. The data show that two Sda molecules bind to the base of the DHp dimerization domain of the KinA dimer. In this position Sda does not appear to be able to sterically block the catalytic domain from accessing its target histidine, as previously proposed, but rather may effect an allosteric mode of inhibition involving transmission of the inhibitory signal via the four-helix bundle that forms the DHp domain.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2007.01.064