Interaction of calmodulin with muscle phosphofructokinase

Abstract

Phosphofructokinase from muscle has been shown to be a calmodulin-binding protein [Mayr, G. W., and Heilmeyer, L. M. G., Jr (1983) FEBS Lett. 159, 51–57]. Details of the influence of calmodulin on the aggregation state, the conformation and the catalytic properties of phosphofructokinase have been studied by enzymatic and light-scattering analyses. Calmodulin acts as a Ca²⁺-dependent hysteretic inhibitor of the highly active enzyme. At least one mole of calmodulin binds to each protomer of the enzyme, induces a shift from the highly active tetrameric towards an inactive dimeric state and slowly changes the conformation of the dimers. Dissociation of calmodulin from conformationally changed dimers by removal of Ca²⁺ stops the inactivation. Without a significant regain of catalytic activity large polymers are rapidly formed. For a reactivation, of the inactivated enzyme, calmodulin has to remain associated and the incubation conditions must be changed in a way to allow for a back isomerization and reassociation of dimers. The isomerization reaction is promoted by Mg · ATP, the reassociation reaction most effectively by fructose bisphosphate. A model for the calmodulin-phosphofructokinase interaction is proposed.