title: Basis of Mutual Domain Inhibition in a Bacterial Response Regulator.
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.
authors.affiliation: Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Corrêa
authors.affiliation: Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031, USA; Department of Chemistry and Biochemistry, City College of New York, New York, NY 10031, USA; Biochemistry, Chemistry and Biology PhD Programs, Graduate Center, The City University of New York, New York, NY 10016, USA. Electronic address: kevin.gardner@asrc.cuny.edu.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Gardner
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction; D042301:Sphingomonadaceae / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins