Basis of Mutual Domain Inhibition in a Bacterial Response Regulator

Fernando Corrêa, Kevin H. Gardner

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)945-955
Number of pages11
JournalCell Chemical Biology
Volume23
Issue number8
DOIs
StatePublished - Aug 18 2016

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Conformations
Proteins
Phosphorylation
Magnetic Resonance Spectroscopy
Chemical activation
Switches
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Drug Discovery
  • Pharmacology

Cite this

Basis of Mutual Domain Inhibition in a Bacterial Response Regulator. / Corrêa, Fernando; Gardner, Kevin H.

In: Cell Chemical Biology, Vol. 23, No. 8, 18.08.2016, p. 945-955.

Research output: Contribution to journalArticle

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