| Title: | Functional Plasticity of the AgrC Receptor Histidine Kinase Required for Staphylococcal Virulence |
| Author(s): | Wang B; Zhao A; Xie Q; Olinares PD; Chait BT; Novick RP; Muir TW; |
| Address: | "Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA; Graduate Program, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA. Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Department of Microbiology, Skirball Institute, NYU Medical Center, 540-562 First Avenue, New York, NY 10016, USA. Department of Chemistry, Frick Chemistry Laboratory, Princeton University, Washington Road, Princeton, NJ 08544-0015, USA. Electronic address: muir@princeton.edu" |
| DOI: | 10.1016/j.chembiol.2016.12.008 |
| ISSN/ISBN: | 2451-9448 (Electronic) 2451-9456 (Print) 2451-9448 (Linking) |
| Abstract: | "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" |
| Keywords: | Bacterial Proteins/*metabolism Protein Kinases/*metabolism Quorum Sensing Staphylococcus aureus/enzymology/*metabolism/*pathogenicity Virulence Staphylococcus aureus agr allelic variation constitutive mutant input-response property nanodisc phospho-transf; |
| Notes: | "MedlineWang, Boyuan Zhao, Aishan Xie, Qian Olinares, Paul Dominic Chait, Brian T Novick, Richard P Muir, Tom W eng P41 GM103314/GM/NIGMS NIH HHS/ R01 AI042783/AI/NIAID NIH HHS/ R01 GM095880/GM/NIGMS NIH HHS/ 2017/01/10 Cell Chem Biol. 2017 Jan 19; 24(1):76-86. doi: 10.1016/j.chembiol.2016.12.008. Epub 2017 Jan 5" |
