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Mechanics of allostery: contrasting the induced fit and population shift scenarios | Riccardo Ravasio
; Solange Flatt
; Le Yan
; Stefano Zamuner
; Carolina Brito
; Matthieu Wyart
; | Date: |
12 Jun 2019 | Abstract: | In allosteric proteins, binding a ligand can affect function at a distant
location, for example by changing the binding affinity of a substrate at the
active site. The induced fit and population shift models, which differ by the
assumed number of stable configurations, explain such cooperative binding from
a thermodynamic viewpoint. Yet, understanding what mechanical principles
constrain these models remains a challenge. Here we provide an empirical study
on 34 proteins supporting the idea that allosteric conformational change
generally occurs along a soft elastic mode presenting extended regions of high
shear. We argue, based on a detailed analysis of how the energy profile along
such a mode depends on binding, that in the induced fit scenario there is an
optimal stiffness $k_a^*sim 1/N$ for cooperative binding, where $N$ is the
number of residues involved in the allosteric response. We find that the
population shift scenario is more robust to mutation affecting stiffness, as
binding becomes more and more cooperative with stiffness up to the same
characteristic value $k_a^*$, beyond which cooperativity saturates instead of
decaying. We confirm numerically these findings in a non-linear mechanical
model. Dynamical considerations suggest that a stiffness of order $k_a^*$ is
favorable in that scenario as well, supporting that for proper function
proteins must evolve a functional elastic mode that is softer as their size
increases. In consistency with this view, we find a significant anticorrelation
between the stiffness of the allosteric response and protein size in our data
set. | Source: | arXiv, 1906.5043 | Services: | Forum | Review | PDF | Favorites |
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