The propagation of allosteric states in large multiprotein complexes

Abstract

A statistical view of allostery leads to a more nuanced and physically realistic picture of protein cooperativity. If the conformational state of one protein molecule in a multiprotein complex influences the probability of a particular conformation in a neighbouring protein, then changes can propagate. Given suitable parameters, linear or two-dimensional arrays of allosteric subunits will then behave similar to an Ising model, exhibiting hypersharp responses to external conditions. Predictions based on this concept find good quantitative agreement in a number of experimental systems including switching of the bacterial flagellar motor, amplification of ligand signals in the Escherichia coli chemotaxis receptors, and termination of calcium sparks in cardiac muscle. A similar mechanism could potentially provide a universal mechanism of integration within living cells.