Possible allosteric effects in extended biological systems

Abstract

Consideration of the behaviour of certain very large invertebrate respiratory proteins, some of which may contain upwards of 100 oxygen binding sites, suggests an allosteric model involving “mixed” conformations. These would result from the fact that each protomer can exist in either one of two forms (or states). Co-operativity is introduced by postulating that the two forms have different oxygen affinities and that the form assumed by any given protomer is dependent on that of the others, presumably as a result of nearest neighbour interactions. This model would account for the very large values of the Hill parameter n over the middle range of saturations coupled with the relatively small values of the total apparent interaction energy shown by these giant molecules. Physically the model is equivalent to that recently proposed by Changeux, Thiery, Tung & Kittel (1967) for biological membranes, in which the number of protomers may be regarded as infinite, and in its application to such infinite systems it predicts the possibility of a ligand linked phase change which is highly sensitive to control by a second ligand. Given suitable values of the parameters, the second ligand might even act to suppress the phase change altogether and “freeze” the system in one phase. It is suggested that this model may have an application to the problem of the propagation of a nerve impulse and its passage across a synapse; also to highly organized enzyme systems present in cells.