Agonists to ions: Efficiency suggests a 'zipper' mechanism for nicotinic receptor activation

Agonists are classified by the strength at which they bind to their target sites (affinity) and their ability to activate receptors once bound to those sites (efficacy). Efficiency is a third fundamental agonist property that is a measure of the correlation between affinity and efficacy. Efficiency is the percent of agonist binding energy that is converted into energy for receptor activation ( gating). In the muscle nicotinic acetylcholine receptor, agonists belong to families having discrete efficiencies of 54%, 51%, 42% or 35%. Efficiency depends on the size and composition of both the agonist and binding site, and can be estimated from, and used to interpret, concentration-response curves. A correlation between affinity and efficacy indicates that the agonists energy changes that take place within binding and gating processes are linked. Efficiency suggests that receptors turn on and off by progressing through a sequence of energy-linked domain rearrangements, as in a zipper.