Sensor domain of histidine kinase KinB of Pseudomonas – a helix-swapped dimer [Signal Transduction]

February 26th, 2014 by Tan, K., Chhor, G., Binkowski, T. A., Jedrzejczak, R. P., Makowska-Grzyska, M., Joachimiak, A.

The overproduction of polysaccharide alginate is responsible for the formation of mucus in the lungs of cystic fibrosis (CF) patients. HK KinB of the KinB-AlgB TCS in Pseudomonas aeruginosa acts as a negative regulator of alginate biosynthesis. The modular architecture of KinB is similar to other HKs. However, its periplasmic signal SD is unique and is found only in the Pseudomonas genus. Here, we present the first crystal structures of the KinB-SD. The domain is a dimer in solution and in the crystal it shows an atypical dimer of a helix-swapped four-helix bundle. A positively charged cavity is formed on the dimer interface and involves several strictly conserved residues, including R60. A phosphate anion is bound asymmetrically in one of the structures. In silico docking identified several monophosphorylated sugars, including β-D-fructose-6-phosphate and [beta]-D-mannose-6-phosphate, a precursor and an intermediate of alginate synthesis, respectively, as potential KinB ligands. Ligand binding was confirmed experimentally. Conformational transition from a symmetric to asymmetric structure and decreasing dimer stability caused by ligand binding may be a part of the signal transduction mechanism of the KinB-AlgB TCS.