Two Ca 2+ ATPase genes: Homologies and mechanistic implications of deduced amino acid sequences

Abstract

Rabbit genomic DNA contains two genes that encode Ca 2+ ATPases of fast twitch and of slow twitch (and cardiac) sarcoplasmic reticulum, respectively. The deduced amino acid sequences of the products of the two genes are highly conserved in putative Ca 2+ binding regions, in sectors leading from cytoplasmic domains into transmembrane domains, and in transmembrane helices. A transport mechanism is proposed in which Ca 2+ binds to negatively charged groups on amphipathic stalk sectors, becoming occluded during enzyme phosphorylation by bound ATP. Rotation of the stalk sectors is induced as the energy in the phosphorylated enzyme (E 1P) is utilized in conformational changes leading to the low energy form, E 2P. Rotation leads to disruption of high affinity Ca 2+ binding sites and release of Ca 2+ into a charge-lined membrane channel. Ca 2+ then traverses the membrane by exchange diffusion.