Allosteric Dynamic Control of Binding

Biophysical Journal
Fidan SumbulTurkan Haliloglu

Abstract

Proteins have a highly dynamic nature and there is a complex interrelation between their structural dynamics and binding behavior. By assuming various conformational ensembles, they perform both local and global fluctuations to interact with other proteins in a dynamic infrastructure adapted to functional motion. Here, we show that there is a significant association between allosteric mutations, which lead to high-binding-affinity changes, and the hinge positions of global modes, as revealed by a large-scale statistical analysis of data in the Structural Kinetic and Energetic Database of Mutant Protein Interactions (SKEMPI). We further examined the mechanism of allosteric dynamics by conducting studies on human growth hormone (hGH) and pyrin domain (PYD), and the results show how mutations at the hinge regions could allosterically affect the binding-site dynamics or induce alternative binding modes by modifying the ensemble of accessible conformations. The long-range dissemination of perturbations in local chemistry or physical interactions through an impact on global dynamics can restore the allosteric dynamics. Our findings suggest a mechanism for the coupling of structural dynamics to the modulation of protein interactions, ...Continue Reading

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Citations

Feb 20, 2016·Chemical Reviews·Nikolay V Dokholyan
Feb 14, 2020·PLoS Computational Biology·Qian-Yuan Tang, Kunihiko Kaneko
Jan 31, 2021·Biophysical Journal·Saliha Ece AcunerTurkan Haliloglu
Apr 14, 2021·The Journal of Physical Chemistry. B·Valentina SoraElena Papaleo
Apr 30, 2021·The Journal of Physical Chemistry. B·Yiǧit KutluTurkan Haliloglu

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