Structure of the skeletal muscle calcium release channel activated with Ca2+ and AMP-PCP

The functional state of the skeletal muscle Ca2+ release channel is modulat ed by a number of endogenous molecules during excitation-contraction. Using electron cryomicroscopy and angular reconstitution techniques, we determin ed the three-dimensional (3D) structure of the skeletal muscle Ca2+ release channel activated by a nonhydrolyzable analog of ATP in the presence of Ca 2+. These ligands together produce almost maximum activation of the channel and drive the channel population toward a predominately open state. The re sulting 30-Angstrom 3D reconstruction reveals long-range conformational cha nges in the cytoplasmic region that might affect the interaction of the Ca2 + release channel with the t-tubule voltage sensor. In addition, a central opening and mass movements, detected in the transmembrane domain of both th e Ca2+- and the Ca2+/nucleotide-activated channels, suggest a mechanism for channel opening similar to opening-closing of the iris in a camera diaphra gm.