Allosteric conformational ensembles have unlimited capacity for integrating information

eLife

John W Biddle¹  Rosa Martinez-Corral¹  Jeremy Gunawardena¹  Felix Wong² 

[1] Department of Systems Biology, Harvard Medical School, Boston, United States;Institute for Medical Engineering and Science, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States;Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, United States;

关键词: allostery;    higher-order coopeartivity;    information integration;    linear framework;    conformational ensembles;    None;   

DOI  :  10.7554/eLife.65498

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY