Probing bacterial transmembrane histidine kinase receptor-ligand interactions with natural and synthetic molecules.

TitleProbing bacterial transmembrane histidine kinase receptor-ligand interactions with natural and synthetic molecules.
Publication TypeJournal Article
Year of Publication2010
AuthorsNg, W-L, Wei, Y, Perez, LJ, Cong, J, Long, T, Koch, M, Semmelhack, MF, Wingreen, NS, Bassler, BL
JournalProc Natl Acad Sci U S A
Volume107
Issue12
Pagination5575-80
Date Published2010 Mar 23
ISSN1091-6490
KeywordsAmino Acid Substitution, Bacterial Proteins, Binding Sites, Genes, Bacterial, Ketones, Ligands, Membrane Proteins, Models, Molecular, Mutagenesis, Mutation, Protein Kinases, Quorum Sensing, Recombinant Fusion Proteins, Signal Transduction, Vibrio cholerae
Abstract

<p>Bacterial histidine kinases transduce extracellular signals into the cytoplasm. Most stimuli are chemically undefined; therefore, despite intensive study, signal recognition mechanisms remain mysterious. We exploit the fact that quorum-sensing signals are known molecules to identify mutants in the Vibrio cholerae quorum-sensing receptor CqsS that display altered responses to natural and synthetic ligands. Using this chemical-genetics approach, we assign particular amino acids of the CqsS sensor to particular roles in recognition of the native ligand, CAI-1 (S-3 hydroxytridecan-4-one) as well as ligand analogues. Amino acids W104 and S107 dictate receptor preference for the carbon-3 moiety. Residues F162 and C170 specify ligand head size and tail length, respectively. By combining mutations, we can build CqsS receptors responsive to ligand analogues altered at both the head and tail. We suggest that rationally designed ligands can be employed to study, and ultimately to control, histidine kinase activity.</p>

DOI10.1073/pnas.1001392107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20212168
PubMed Central IDPMC2851778
Grant List5R01AI054442 / AI / NIAID NIH HHS / United States
GM082061 / GM / NIGMS NIH HHS / United States
R01 AI054442 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States