Title | Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Wang, B, Zhao, A, Xie, Q, Olinares, PDominic, Chait, BT, Novick, RP, Muir, TW |
Journal | Cell Chem Biol |
Volume | 24 |
Issue | 1 |
Pagination | 76-86 |
Date Published | 2017 Jan 19 |
ISSN | 2451-9448 |
Keywords | Bacterial Proteins, Protein Kinases, Quorum Sensing, Staphylococcus aureus, Virulence |
Abstract | <p>Staphylococcus aureus employs the receptor histidine kinase (RHK), AgrC, to detect quorum-sensing (QS) pheromones, the autoinducer peptides (AIPs), which regulate the virulence of the bacterium. Variation in the QS circuit divides S. aureus into four subgroups, each producing a specific AIP-AgrC pair. While the timing of QS induction is known to differ among these subgroups, the molecular basis of this phenomenon is unknown. Here, we report the successful reconstitution of several AgrC variants and show that the agonist-induced activity of the receptors varies in a manner that accounts for these temporal differences in QS induction. Our studies also reveal a key regulatory hotspot on AgrC that controls the basal activity of RHK as well as the responsiveness of the system to ligand inputs. Collectively, these studies offer insights into the capacity of the RHK for adaptive evolution.</p> |
DOI | 10.1016/j.chembiol.2016.12.008 |
Alternate Journal | Cell Chem Biol |
PubMed ID | 28065658 |
PubMed Central ID | PMC5697745 |
Grant List | P41 GM103314 / GM / NIGMS NIH HHS / United States R01 AI042783 / AI / NIAID NIH HHS / United States R01 GM095880 / GM / NIGMS NIH HHS / United States |