Structure-function relationships in adenylate cyclase systems.

Hormone-sensitive adenylate cyclase systems are composed of hormone-recognition units (R), a nucleotide-regulatory unit (N) for reaction with GTP and divalent cations, and the catalytic unit (C). From the reported sizes of purified R and N subunits and target analysis of functional sizes of these units, the functions of the components for the binding and actions of hormones and GTP require minimally dimers, homologous or heterologous. It is proposed that the catalytic unit exists in the membrane also as a dimer and that its transition to the active state with MgATP as substrate involves corresponding transitions in linked dimers of the hormone-recognition and nucleotide-regulatory units. It is postulated that hormones trigger the activation process by inducing in concert with GTP and divalent cations the appropriate dimer structure of the holoenzyme. In large aggregates of such structures, realignment of only a few occupied holoenzyme units may be sufficient to induce activation of the total aggregate enzyme. This theory serves to explain the synergistic actions of hormones, and how several hormones can activate a common enzyme. It also provides an explanation for 'spare' receptors, and for the efficacy of hormone action.