title: Structure of the cytoplasmic segment of histidine kinase receptor QseC, a key player in bacterial virulence.
abstract: QseC is a histidine kinase (HK) receptor involved in quorum sensing, a mechanism by which bacteria respond to fluctuations in cell population. We conducted a structural study of the cytoplasmic domain of QseC (QseC-CD) using X-ray crystallography. The 2.5 Å structure of the apo-enzyme revealed that the kinase domain of QseC retains the overall fold of the typical HK kinase domain. The construct that we used is inactive in the autokinase reaction and its inactivity is most likely caused by its atypical dimerization interface, as compared to that observed in the T.maritima HK cytoplasmic domain structure. Restoration of the activity may require that the entire dimerization domain be present in the protein construct. QseC, which plays an important role in bacterial pathogenesis, is a promising drug target and the structure of QseC-CD provides a platform for developing more potent inhibitors of pathogen virulence.
authors.affiliation: Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Chris
authors.initials: C
authors.lastname: Dickson
authors.forename: Witek
authors.initials: W
authors.lastname: Kwiatkowski
authors.forename: Senyon
authors.initials: S
authors.lastname: Choe
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000737:chemistry*; D000071677:Histidine Kinase; D008958:Models, Molecular; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D020124:Thermotoga maritima / Q000201:enzymology
chemical_list: D029968:Escherichia coli Proteins; C455504:QseC protein, E coli; D011494:Protein Kinases; D000071677:Histidine Kinase