Conformational spread in a ring of proteins: A stochastic approach to allostery

We recently suggested that the sensitivity and range of a cluster of membra ne receptors in bacteria would be enhanced by cooperative interactions betw een neighbouring proteins. Here, we examine the consequences of this "confo rmational spread" mechanism for an idealised one-dimensional system compris ing a closed ring of identical allosteric protomers (protein molecules, or a group of protein domains operating as a unit). We show analytically and b y means of Monte Carlo simulations that a ring of allosteric protomers can exhibit a switch-like response to changes in ligand concentration. We deriv e expressions for the sensitivity and cooperativity of switching and show t hat the maximum sensitivity is proportional to the number of protomers in t he ring. A ring of this kind can reproduce the sensitivity and kinetics of the switch complex of a bacterial flagellar motor, for example, which is ba sed on a ring of 34 FliM proteins. We also compare smaller rings of conform ationally coupled protomers to classical allosteric proteins such as haemog lobin and show that the canonical MWC and KNF models arise naturally as lim iting cases. Conformational spread appears to be a natural extension of the familiar mechanism of allostery: a physically realistic mechanism that sho uld apply widely to many structures built from protein molecules. (C) 2001 Academic Press.