Calcium-calmodulin interaction and cellular function.

Abstract

Conformational and functional events in calmodulin (CaM) are directly governed by the degree of saturation by Ca2+, and do not depend on Ca2+-occupancy of any particular one of the four ion-binding sites. For instance, the exposure of a hydrophobicity at the surface of the protein coincides with the appearance of CaM X Can greater than or equal to 2. The species containing at least three Ca2+ is most often involved in target enzyme activation. The activation parameters explain the "on-off" behavior of the CaM-activated systems, in spite of the small amplitude of Ca2+-transients in stimulated cells. The strong energy coupling involved in activation is at the basis of a hysteretic behavior of the cell response: after the decay of free cytoplasmic Ca2+, the dissociation of the ternary complex between enzyme, CaM, and Ca2+ is delayed. Studying natural and synthetic model peptides that interact with CaM, we hope to obtain new insight into the CaM-binding domain in the different target enzymes. The minimal and sufficient requirement for high-affinity interaction of model peptides with CaM is a basic amphiphilic alpha-helix of at least 18 A. Preliminary data on the secondary structure of target enzymes indicate that their CaM-binding domains may have these structural requirements.