@article{3518,
  keywords = {Quorum Sensing, Bacterial Proteins, Humans, Protein Kinases, Signal Transduction, Virulence, Staphylococcus aureus, Protein Conformation, Hydrogen Bonding, Allosteric Regulation, Peptides, Cyclic, Molecular Docking Simulation, Staphylococcal Infections},
  author = {Qian Xie and Aishan Zhao and Philip Jeffrey and Minyoung Kim and Bonnie Bassler and Howard Stone and Richard Novick and Tom Muir},
  title = {Identification of a Molecular Latch that Regulates Staphylococcal Virulence.},
  abstract = { <p>Virulence induction in the Staphylococcus aureus is under the control of a quorum sensing (QS) circuit encoded by the accessory gene regulator (agr) locus. Allelic variation within agr produces four QS specificity groups, each producing a unique secreted autoinducer peptide (AIP) and receptor histidine kinase (RHK), AgrC. Cognate AIP-AgrC interactions activate virulence through a two-component signaling cascade, whereas non-cognate pairs are~generally inhibitory. Here we pinpoint a key hydrogen-bonding interaction within AgrC that acts as a switch to convert helical motions propagating from the receptor sensor domain into changes in inter-domain association within the kinase module. AgrC mutants lacking this interaction are constitutively active in~vitro and in~vivo, the latter leading to a pronounced attenuation of S.~aureus biofilm formation. Thus, our work sheds light on the regulation of this biomedically important RHK.</p> },
  year = {2019},
  journal = {Cell Chem Biol},
  volume = {26},
  pages = {548-558.e4},
  month = {2019 Apr 18},
  issn = {2451-9448},
  doi = {10.1016/j.chembiol.2019.01.006},
  language = {eng},
}