The structure of the Legionella response regulator LqsR reveals amino acids critical for phosphorylation and dimerization

Mol Microbiol. 2020 Jun;113(6):1070-1084. doi: 10.1111/mmi.14477. Epub 2020 Feb 12.


The water-borne bacterium Legionella pneumophila replicates in environmental protozoa and upon inhalation destroys alveolar macrophages, thus causing a potentially fatal pneumonia termed 'Legionnaires' disease'. L. pneumophila employs the Legionella quorum sensing (Lqs) system to control its life cycle, pathogen-host cell interactions, motility and natural competence. Signaling through the Lqs system occurs through the α-hydroxyketone compound Legionella autoinducer-1 (LAI-1) and converges on the prototypic response regulator LqsR, which dimerizes upon phosphorylation of the conserved aspartate, D108 . In this study, we determine the high-resolution structure of monomeric LqsR. The structure reveals a receiver domain adopting a canonical (βα)5 fold, which is connected through an additional sixth helix and an extended α5-helix to a novel output domain. The two domains delineate a mainly positively charged groove, and the output domain adopts a five-stranded antiparallel β-sheet fold similar to nucleotide-binding proteins. Structure-based mutagenesis identified amino acids critical for LqsR phosphorylation and dimerization. Upon phosphorylation, the LqsRD172A and LqsRD302N/E303Q mutant proteins dimerized even more readily than wild-type LqsR, and no evidence for semi-phosphorylated heterodimers was obtained. Taken together, the high-resolution structure of LqsR reveals functionally relevant amino acid residues implicated in signal transduction of the prototypic response regulator.

Keywords: Legionella; autoinducer; bacterial pathogenesis; c-di-GMP; cell-cell signaling; oligomerization; phospho-transfer; quorum sensing; response regulator; sensor kinase; α-hydroxyketone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Dimerization
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Host-Pathogen Interactions / physiology
  • Legionella pneumophila / genetics
  • Legionella pneumophila / metabolism*
  • Locomotion / physiology
  • Phosphorylation / physiology
  • Protein Folding
  • Protein Structure, Tertiary
  • Quorum Sensing / physiology*
  • Response Elements / genetics*
  • Response Elements / physiology*