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Coarse‐grained dynamics of the receiver domain of NtrC: Fluctuations, correlations and implications for allosteric cooperativity
Author(s) -
Liu Ming S.,
Todd B. D.,
Yao Shenggen,
Feng ZhiPing,
Norton Raymond S.,
Sadus Richard J.
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22056
Subject(s) - allosteric regulation , cooperativity , phosphorylation , chemistry , molecular dynamics , biophysics , flexibility (engineering) , active site , conformational change , protein dynamics , stereochemistry , biology , biochemistry , computational chemistry , mathematics , statistics , enzyme
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. Proteins 2008. © 2008 Wiley‐Liss, Inc.