Fernando Corrêa and Kevin H. Gardner
Cell Chemical Biology
2016 vol: 23 issue: 8 pp:945-954 doi: 10.1016/j.chembiol.2016.07.010
Abstract
Information transmission in biological signaling networks is commonly considered to be a unidirectional flow of information between protein partners. According to this view, many bacterial response regulator proteins utilize input receiver (REC) domains to “switch” functional outputs, using REC phosphorylation to shift pre-existing equilibria between inactive and active conformations. However, recent data indicate that output domains themselves also shift such equilibria, implying a “mutual inhibition” model. Here we use solution nuclear magnetic resonance to provide a mechanistic basis for such control in a PhyR-type response regulator. Our structure of the isolated, non-phosphorylated REC domain surprisingly reveals a fully active conformation, letting us identify structural and dynamic changes imparted by the output domain to inactivate the full-length protein. Additional data reveal transient structural changes within the full-length protein, facilitating activation. Our data provide a basis for understanding the changes that REC and output domains undergo to set a default “inactive” state.
Topics: Nuclear Magnetic Resonance, Biomolecular, Phosphorylation, Protein Conformation, Signal Transduction, Monolith – MicroScale Thermophoresis, MST, Proteins, Publications
