BIOCHEMISTRY: Lifting a Switch

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Science  13 Jan 2006:
Vol. 311, Issue 5758, pp. 147a
DOI: 10.1126/science.311.5758.147a

Two-component systems enable microbes to respond to environmental conditions. Signal transduction begins when a dimeric integral membrane protein senses an external signal, and one of the monomers phosphorylates the other on a histidine residue. Thisphosphoryl group is then transferred to the cytosolic response regulator protein, which initiates changes in gene expression. Salmonella typhimurium PhoPQ promotes virulence of this pathogen in humans, and the activity of the sensor component PhoQ can be repressed by divalent cations, such as calcium and magnesium.

Cho et al. describe the structure of the external domain of PhoQ, with four monomers in the asymmetric unit of the crystal. They find that two of the monomers associate in a fashion similar to what would be expected for the in vivo PhoQ dimer and that together they display a planar surface rich in acidic residues. Biochemical and structural experiments pinpoint at least three calcium-binding sites per monomer on this surface, which would allow the dimer to lie flat on top of the negatively charged head groups of the lipid bilayer. This positioning leads the authors to propose that displacement of the divalent ions (for instance, by cationic antibiotic peptides) would trigger a lever-like movement of the sensor domain up off of the membrane surface, thereby turning on the kinase. — GJC

J. Mol. Biol. 10.1016/j.jmb.2005.12.032 (2005).

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