Calcium transport across the sarcoplasmic reticulum - Structure and function of Ca2+-ATPase and the ryanodine receptor

Contraction of striated muscle results from a rise in cytoplasmic calcium c oncentration in a process termed excitation/contraction coupling. Most of t his calcium moves back and forth across the sarcoplasmic-reticulum membrane in cycles of contraction and relaxation. The channel responsible for relea se from the sarcoplasmic reticulum is the ryanodine receptor, whereas Ca2+- ATPase effects reuptake in an ATP-dependent manner. The structures of these two molecules have been studied by cryoelectron microscopy, with helical c rystals in the case of Ca2+-ATPase and as isolated tetramers in the case of ryanodine receptor. Structures of Ca2+-ATPase at 8-Angstrom resolution rev eal the packing of transmembrane helices and have allowed fitting of a puta tive ATP-binding domain among the cytoplasmic densities. Comparison of ATPa ses in different conformations gives hints about the conformational changes that accompany the reaction cycle. Structures of ryanodine receptor at 30- Angstrom resolution reveal a multitude of isolated domains in the cytoplasm ic portion, as well as a distinct transmembrane assembly. Binding sites for various protein ligands have been determined and conformational changes in duced by ATP, calcium and ryanodine have been characterized. Both molecules appear to use large conformational changes to couple interactions in their cytoplasmic domains with calcium transport through their membrane domains, and future studies at higher resolution will focus on the mechanisms for t his coupling.