Ligand and antagonist driven regulation of the Vibrio cholerae quorum-sensing receptor CqsS.

TitleLigand and antagonist driven regulation of the Vibrio cholerae quorum-sensing receptor CqsS.
Publication TypeJournal Article
Year of Publication2012
AuthorsWei, Y, Ng, W-L, Cong, J, Bassler, BL
JournalMol Microbiol
Volume83
Issue6
Pagination1095-108
Date Published2012 Mar
ISSN1365-2958
KeywordsBacterial Proteins, Cholera, Gene Expression Regulation, Bacterial, Histidine Kinase, Humans, Ketones, Ligands, Phosphoproteins, Phosphorylation, Protein Binding, Protein Kinases, Protein Structure, Tertiary, Quorum Sensing, Repressor Proteins, Vibrio cholerae
Abstract

<p>Quorum sensing, a bacterial cell-cell communication process, controls biofilm formation and virulence factor production in Vibrio cholerae, a human pathogen that causes the disease cholera. The major V. cholerae autoinducer is (S)-3-hydroxytridecan-4-one (CAI-1). A membrane bound two-component sensor histidine kinase called CqsS detects CAI-1, and the CqsS → LuxU → LuxO phosphorelay cascade transduces the information encoded in CAI-1 into the cell. Because the CAI-1 ligand is known and because the signalling circuit is simple, consisting of only three proteins, this system is ideal for analysing ligand regulation of a sensor histidine kinase. Here we reconstitute the CqsS → LuxU → LuxO phosphorylation cascade in vitro. We find that CAI-1 inhibits the initial auto-phosphorylation of CqsS whereas subsequent phosphotransfer steps and CqsS phosphatase activity are not CAI-1-controlled. CAI-1 binding to CqsS causes a conformational change that renders His194 in CqsS inaccessible to the CqsS catalytic domain. CqsS mutants with altered ligand detection specificities are faithfully controlled by their corresponding modified ligands in vitro. Likewise, pairing of agonists and antagonists allows in vitro assessment of their opposing activities. Our data are consistent with a two-state model for ligand control of histidine kinases.</p>

DOI10.1111/j.1365-2958.2012.07992.x
Alternate JournalMol Microbiol
PubMed ID22295878
PubMed Central IDPMC3310172
Grant ListR01 GM065859 / GM / NIGMS NIH HHS / United States
5R01AI054442 / AI / NIAID NIH HHS / United States
R01 AI054442 / AI / NIAID NIH HHS / United States
R01 GM065859-10 / GM / NIGMS NIH HHS / United States
5R01GM065859 / GM / NIGMS NIH HHS / United States
/ HHMI_ / Howard Hughes Medical Institute / United States