Coarse-grained dynamics of the receiver domain of NtrC: Fluctuations, correlations and implications for allosteric cooperativity
- Details
- Publication Year 2008-10,Volume 73,Issue #1,Page 218-227
- Journal Title
- PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
- Publication Type
- Journal Article
- Abstract
- Receiver domains are key molecular switches ill 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 tire inactive state to tire active state. Tire diagonalized correlation between the inactive and tire active (phosphorylated) state shows that most correlated motions occur around the active site of Asp54 and in tire region Thr82 to Tyr101. This indicates a coupled correlation of dynamics in tire "Thr-82-Tyr101" motion. With phosphorylation inducing significant flexibility changes around tire active site and alpha 3 and alpha 4 helices, we find that this activation makes the active-site region and the loops of alpha 3/beta 4 and alpha 4/beta 5 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 file allosteric cooperativity of NtrC, and may be applicable to other proteins.
- Publisher
- WILEY-LISS
- Keywords
- NORMAL-MODE ANALYSIS; TRANSITION-STATE ENSEMBLE; FREQUENCY NORMAL-MODES; SIGNAL-TRANSDUCTION; MOLECULAR-DYNAMICS; CONFORMATIONAL-CHANGE; INTRINSIC MOTIONS; NETWORK MODEL; PROTEIN; MOTOR
- Publisher's Version
- https://doi.org/10.1002/prot.22056
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- Refer to copyright notice on published article.
Creation Date: 2008-10-01 12:00:00