Symmetric signalling within asymmetric dimers of the Staphylococcus aureus receptor histidine kinase AgrC.
Virulence in Staphylococcus aureus is largely under control of the accessory gene regulator (agr) quorum-sensing system. The AgrC receptor histidine kinase detects its autoinducing peptide (AIP) ligand and generates an intracellular signal resulting in secretion of virulence factors. Although agr is a well-studied quorum-sensing system, little is known about the mechanism of AgrC activation. By co-immunoprecipitation analysis and intermolecular complementation of receptor mutants, we showed that AgrC forms ligand-independent dimers that undergo trans-autophosphorylation upon interaction with AIP. Remarkably, addition of specific AIPs to AgrC mutant dimers with only one functional sensor domain caused symmetric activation of either kinase domain despite the sensor asymmetry. Furthermore, mutant dimers involving one constitutive protomer demonstrated ligand-independent activity, irrespective of which protomer was kinase deficient. These results demonstrate that signalling through either individual AgrC protomer causes symmetric activation of both kinase domains. We suggest that such signalling across the dimer interface may be an important mechanism for dimeric quorum-sensing receptors to rapidly elicit a response upon signal detection.
George Cisar
Elizabeth A
EA
Laboratory of Synthetic Protein Chemistry, Training Program in Chemical Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.Molecular Pathogenesis Program and Departments of Microbiology and Medicine, the Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Geisinger
Edward
E
Laboratory of Synthetic Protein Chemistry, Training Program in Chemical Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.Molecular Pathogenesis Program and Departments of Microbiology and Medicine, the Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Muir
Tom W
TW
Laboratory of Synthetic Protein Chemistry, Training Program in Chemical Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.Molecular Pathogenesis Program and Departments of Microbiology and Medicine, the Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Novick
Richard P
RP
Laboratory of Synthetic Protein Chemistry, Training Program in Chemical Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.Molecular Pathogenesis Program and Departments of Microbiology and Medicine, the Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D053038:Quorum Sensing; D016415:Sequence Alignment; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
D001426:Bacterial Proteins; D011494:Protein Kinases; C531166:AgrC protein, Staphylococcus