Allosteric conformational ensembles have unlimited capacity for integrating information

• Published in: eLife Vol. 10
• Main Authors: Biddle, John W, Martinez-Corral, Rosa, Wong, Felix, Gunawardena, Jeremy
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 09.06.2021; eLife Sciences Publications, Ltd
• Subjects: Allosteric properties; Allosteric Regulation - physiology; allostery; Animals; Binding sites; Biophysical Phenomena; conformational ensembles; Energy expenditure; Gene Expression Regulation; Gene regulation; Hemoglobin; higher-order coopeartivity; information integration; Integration; Ligands; linear framework; Machine Learning; Macromolecules; Models, Biological; Physics of Living Systems; Protein Binding - physiology; Protein Conformation; Structural Biology and Molecular Biophysics; higher-order coopeartivity; conformational ensembles; information integration; linear framework; structural biology; none; molecular biophysics; physics of living systems; allostery
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.65498

Integration of binding information by macromolecular entities is fundamental to cellular functionality. Recent work has shown that such integration cannot be explained by pairwise cooperativities, in which binding is modulated by binding at another site. Higher-order cooperativities (HOCs), in which binding is collectively modulated by multiple other binding events, appear to be necessary but an appropriate mechanism has been lacking. We show here that HOCs arise through allostery, in which effective cooperativity emerges indirectly from an ensemble of dynamically interchanging conformations. Conformational ensembles play important roles in many cellular processes but their integrative capabilities remain poorly understood. We show that sufficiently complex ensembles can implement any form of information integration achievable without energy expenditure, including all patterns of HOCs. Our results provide a rigorous biophysical foundation for analysing the integration of binding information through allostery. We discuss the implications for eukaryotic gene regulation, where complex conformational dynamics accompanies widespread information integration.