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Cell Chem Biol. 2016 Aug 18;23(8):945-954. doi: 10.1016/j.chembiol.2016.07.010. Epub 2016 Aug 11.

Basis of Mutual Domain Inhibition in a Bacterial Response Regulator.

Author information

1
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031, USA.
2
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.

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.

PMID:
27524295
PMCID:
PMC5159254
DOI:
10.1016/j.chembiol.2016.07.010
[Indexed for MEDLINE]
Free PMC Article

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