research advances
September 2008 research highlight
Sensing tetroses
PSI-SGKB [doi:10.1038/rhighlts_psisgkb.2008.2]
Sensor domains of DcuS (green) and DctB (blue).
Two-component systems play a central role in the ability of bacteria to respond to environmental changes. They are composed of two elements - a transmembrane sensor kinase and a cytoplasmic response regulator. The former contains a modular periplasmic domain that recognizes specific ligands and a conserved cytoplasmic kinase that undergoes autophosphorylation upon ligand binding. The phosphate is then transferred to the cytoplasmic response regulator. To gain insight into ligand sensing by two-component systems, Cheung and Hendrickson solved the crystal structures of periplasmic domains from two sensor kinases: DcuS from Escherichia coli and DctB from Vibrio cholerae. Both domains recognize C4-dicarboxylates, but the DcuS domain is only 140 aa, compared to 270 residues in DctB. The DctB structure showed two subdomains with similar folds (r.s.m.d. of 1.37 Å for 56 Cα positions). The smaller DcuS is also similar, and could be superimposed onto either of DctB's subdomains (r.s.m.d. of 1.54 Å from 115 Cα positions with the proximal one and of 1.68 Å from 67 Cα positions with the distal one), and all are similar in fold to the sensor domains from citrate sensor CitA and magnesium sensor PhoQ, although sequence similarity is low. This structural similarity led the authors to define the PDC (for PhoQ-DcuS-CitA) fold, which differs from the 4-helix bundles seen in sensor domains from aspartate receptor Tar and nitrate sensor NarX. The DcuS domain was crystallized with its ligand malate, and the structure shows that the interactions occur via direct and water-mediated hydrogen bonds, as well as hydrophobic interactions. The DctB sensor domain structure showed a succinate molecule, presumably from E. coli cytosol, bound to the distal subdomain, via interactions similar to those in the DcuS-malate complex. Protein loops surround the ligand pockets from DcuS and DctB, indicating that ligand-dependent conformational changes are likely to occur. Thus this work provides an initial step in understanding how these periplasmic ligands cause activation of the kinase domain.
