6SY9

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

(2020) Mol Microbiol 113: 1070-1084

• PubMed: 31997467 Search on PubMed
• DOI: https://doi.org/10.1111/mmi.14477
• Primary Citation of Related Structures:  
  6SY9


• PubMed Abstract: 
  

  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, D ₁₀₈ . 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 LqsR _D172A and LqsR _D302N/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.

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Organizational Affiliation: 

Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland.