2019/06/30 by Riccardo Ravasio, Solange Flatt, Solange Marie Flatt +4 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Materials Science · Mathematics · Physics and Astronomy · #Allosteric enzyme #Allosteric regulation #Binding site #Biology #Biophysics #Chemistry #Consistency (knowledge bases) #Cooperative binding #Cooperativity #Enzyme Structure and Function #Evolutionary biology #Function (biology) #Geometry #Hemoglobin structure and function #Mathematics #Physics #Population #Protein Structure and Dynamics #Receptor #Statistical physics #Stiffness #Thermodynamics #cond-mat.soft #physics.bio-ph
paper · pdf · doi:10.1016/j.bpj.2019.10.002
openalex publication_date 2019/10/09 · crossref created 2019/10/09 · arxiv created 2019/10/25 · arxiv updated 2019/10/28 · crossref issued 2019/11/01 · crossref published 2019/11/01 · crossref published-print 2019/11/01 · openalex created_date 2025/10/10 · crossref deposited 2026/05/13 · crossref indexed 2026/08/01 · openalex updated_date 2026/08/05
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 ka^*∼ 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 ka^*, 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 ka^* 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.