The role of slow and fast protein motions in allosteric interactions

Biophysics Reviews
Shiou-Ru Tzeng, Charalampos G Kalodimos

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.

References

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Nov 20, 2009·Nature·Shiou-Ru Tzeng, Charalampos G Kalodimos
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Dec 15, 2011·Methods in Molecular Biology·Shiou-Ru TzengCharalampos G Kalodimos
Jan 20, 2012·Annals of the New York Academy of Sciences·Charalampos G Kalodimos
Jul 18, 2012·Nature·Shiou-Ru Tzeng, Charalampos G Kalodimos
May 7, 2013·Nature Chemical Biology·Shiou-Ru Tzeng, Charalampos G Kalodimos

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Citations

Mar 23, 2018·Physical Chemistry Chemical Physics : PCCP·Neeladri Sekhar RoySiddhartha Roy
Nov 24, 2018·Frontiers in Molecular Biosciences·Kathleen F O'RourkeDavid D Boehr
Nov 11, 2020·Current Opinion in Structural Biology·Tobias KrojerFrank von Delft
Jul 27, 2021·Journal of Magnetic Resonance·Ahallya JaladeepAshok Sekhar

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