Coarse-grained dynamics of the receiver domain of NtrC: Fluctuations, correlations and implications for allosteric cooperativity

Ming S. Liu, B. D. Todd, Shenggen Yao, Zhi Ping Feng, Raymond S. Norton, Richard J. Sadus

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11 Citations (Scopus)

Abstract

Receiver domains are key molecular switches in bacterial signaling. Structural studies have shown that the receiver domain of the nitrogen regulatory protein C (NtrC) exists in a conformational equilibrium encompassing both inactive and active states, with phosphorylation of Asp54 allosterically shifting the equilibrium towards the active state. To analyze dynamical fluctuations and correlations in NtrC as it undergoes activation, we have applied a coarse-grained dynamics algorithm using elastic network models. Normal mode analysis reveals possible dynamical pathways for the transition of NtrC from the inactive state to the active state. The diagonalized correlation between the inactive and the active (phosphorylated) state shows that most correlated motions occur around the active site of Asp54 and in the region Thr82 to Tyr101. This indicates a coupled correlation of dynamics in the "Thr82-Tyr101" motion. With phosphorylation inducing significant flexibility changes around the active site and α3 and α4 helices, we find that this activation makes the active-site region and the loops of α3/β4 and α4/β5 more stable. This means that phosphorylation entropically favors the receiver domain in its active state, and the induced conformational changes occur in an allosteric manner. Analyses of the local flexibility and long-range correlated motion also suggest a dynamics criterion for determining the allosteric cooperativity of NtrC, and may be applicable to other proteins.

Original languageEnglish
Pages (from-to)218-227
Number of pages10
JournalProteins: Structure, Function and Bioinformatics
Volume73
Issue number1
DOIs
Publication statusPublished - Oct 2008
Externally publishedYes

Keywords

  • Allosteric cooperativity
  • Coarse-grained dynamics
  • Dynamical correlation
  • Flexibility
  • Intrinsic fluctuation
  • Nitrogen regulatory protein C (NtrC)
  • Normal mode analysis
  • Two-component system

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