Sensor domain of histidine kinase KinB of Pseudomonas: a helix-swapped dimer.

Kemin Tan, Gekleng Chhor, T Andrew Binkowski, Robert P Jedrzejczak, Magdalena Makowska-Grzyska, Andrzej Joachimiak

Journal: The Journal of biological chemistry 2014;289(18):12232-44

PMID: 24573685

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Abstract

The overproduction of polysaccharide alginate is responsible for the formation of mucus in the lungs of cystic fibrosis patients. Histidine kinase KinB of the KinB-AlgB two-component system in Pseudomonas aeruginosa acts as a negative regulator of alginate biosynthesis. The modular architecture of KinB is similar to other histidine kinases. However, its periplasmic signal sensor domain is unique and is found only in the Pseudomonas genus. Here, we present the first crystal structures of the KinB sensor domain. 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 Arg-60. 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 β-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 an asymmetric structure and decreasing dimer stability caused by ligand binding may be a part of the signal transduction mechanism of the KinB-AlgB two-component system.

Address: From the Midwest Center for Structural Genomics and.

DOI: 10.1074/jbc.M113.514836

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MeSH Terms: Alginates, Amino Acid Sequence, Bacterial Proteins, Binding Sites, Circular Dichroism, Crystallography, X-Ray, DNA-Binding Proteins, Fructosephosphates, Glucuronic Acid, Hexuronic Acids, Histidine Kinase, Ligands, Mannosephosphates, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Kinases, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Pseudomonas aeruginosa, Sequence Homology, Amino Acid, Transcription Factors