Determinants governing ligand specificity of the Vibrio harveyi LuxN quorum-sensing receptor.

TitleDeterminants governing ligand specificity of the Vibrio harveyi LuxN quorum-sensing receptor.
Publication TypeJournal Article
Year of Publication2015
AuthorsKe, X, Miller, LC, Bassler, BL
JournalMol Microbiol
Date Published2015 Jan
Keywords4-Butyrolactone, Bacterial Proteins, Binding Sites, Histidine, Leucine, Protein Kinases, Quorum Sensing, Signal Transduction, Substrate Specificity, Transcription Factors, Vibrio

<p>Quorum sensing is a process of bacterial cell-cell communication that relies on the production, release and receptor-driven detection of extracellular signal molecules called autoinducers. The quorum-sensing bacterium Vibrio harveyi exclusively detects the autoinducer N-((R)-3-hydroxybutanoyl)-L-homoserine lactone (3OH-C4 HSL) via the two-component receptor LuxN. To discover the principles underlying the exquisite selectivity LuxN has for its ligand, we identified LuxN mutants with altered specificity. LuxN uses three mechanisms to verify that the bound molecule is the correct ligand: in the context of the overall ligand-binding site, His210 validates the C3 modification, Leu166 surveys the chain-length and a strong steady-state kinase bias imposes an energetic hurdle for inappropriate ligands to elicit signal transduction. Affinities for the LuxN kinase on and kinase off states underpin whether a ligand will act as an antagonist or an agonist. Mutations that bias LuxN to the agonized, kinase off, state are clustered in a region adjacent to the ligand-binding site, suggesting that this region acts as the switch that triggers signal transduction. Together, our analyses illuminate how a histidine sensor kinase differentiates between ligands and exploits those differences to regulate its signaling activity.</p>

Alternate JournalMol Microbiol
PubMed ID25367076
PubMed Central IDPMC4275348
Grant ListR01 GM065859 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
5R01GM065859 / GM / NIGMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States