Allosteric conformational ensembles have unlimited capacity for integrating information.

John W Biddle,Rosa Martinez-Corral,Jeremy Gunawardena,Felix Wong

doi:10.7554/elife.65498

Abstract

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.

Highlights

Cells receive information in different ways, of which molecular binding is the most diverse and widespread
We show that allosteric conformational ensembles can implement any pattern of effective Higher-order cooperativities (HOCs)
A suitable biochemical system is described by a finite directed graph with labelled edges

Summary

Introduction

Cells receive information in different ways, of which molecular binding is the most diverse and widespread. (In considering the target of binding, we use ‘molecule’ for simplicity to denote any molecular entity, from a single polypeptide to a macromolecular aggregate such as an oligomer or complex with multiple components.) We use the notation Ki;S for the association constant—on-rate divided by offrate, with dimensions of (concentration)À1—where i denotes the binding site and S denotes the set of sites which are already bound. This notation was introduced in previous work (Estrada et al, 2016) and is explained further in the Materials and methods. A convenient choice vertically is those association constants Kck;i;S with i less than all the sites in S, denoted i

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Conclusion