Structural and Mechanistic Implications of the Amino Acid Sequence of Calcium‐Transporting ATPases

Publisher Website
Google Scholar
Abstract
Work is reviewed in which the amino acid sequences of two Ca2+-transporting ATPases of sarcoplasmic reticulum (SR) from slow (or cardiac) and fast skeletal muscle were determined from the nucleotide sequences of cloned cDNAs. Analysis of hydrophobicity and secondary structure, combined with the known shape derived from electron micrographs, leads to a model of five domains with functional implications. The major globular part of the molecule is in the cytoplasm and consists of one antiparallel and two parallel β-sheet domains. One of the latter binds ATP, which, in the presence of Ca2+, phosphorylates an aspartic acid on the other domain. It is proposed that subsequent kinase-like movements are transmitted to the SR membrane via a penta-helical, calcium-binding stalk. The Ca2+ is first trapped and then translocated via the ten helices which constitute the transmembrane (channel) region. The difference in requirements for counter ions between the Ca2+- and Na+/K+-ATPases can be explained in terms of differing charge distributions in this channel.