Abstract
Allostery is fundamentally thermodynamic in nature. Long-range communication in proteins may be mediated not only by changes in the mean conformation with enthalpic contribution but also by changes in dynamic fluctuations with entropic contribution. The important role of protein motions in mediating allosteric interactions has been established by NMR spectroscopy. By using CAP as a model system, we have shown how changes in protein structure and internal dynamics can allosterically regulate protein function and activity. The results indicate that changes in conformational entropy can give rise to binding enhancement, binding inhibition, or have no effect in the expected affinity, depending on the magnitude and sign of enthalpy–entropy compensation. Moreover, allosteric interactions can be regulated by the modulation a low-populated conformation states that serve as on-pathway intermediates for ligand binding. Taken together, the interplay between fast internal motions, which are intimately related to conformational entropy, and slow internal motions, which are related to poorly populated conformational states, can regulate protein activity in a way that cannot be predicted on the basis of the protein’s ground-state structure.
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This work was supported by the US National Science Foundation grant MCB1121896 to C.G.K.
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S.-R. Tzeng and C.G. Kalodimos declare that they have no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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This article is part of a Special Issue on 'The Role of Protein Dynamics in Allosteric Effects' edited by Gordon Roberts.
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Tzeng, SR., Kalodimos, C.G. The role of slow and fast protein motions in allosteric interactions. Biophys Rev 7, 251–255 (2015). https://doi.org/10.1007/s12551-015-0172-8
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DOI: https://doi.org/10.1007/s12551-015-0172-8