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 modulated by a number of endogenous molecules during excitation-contraction. Using electron cryomicroscopy and angular reconstitution techniques, we determined the three-dimensional (3D) structure of the skeletal muscle Ca2+ release channel activated by a nonhydrolyzable analog of ATP in the presence of Ca2+. These ligands together produce almost maximum activation of the channel and drive the channel population toward a predominately open state. The resulting 30-A 3D reconstruction reveals long-range conformational changes 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 the Ca(2+)- and the Ca2+/nucleotide-activated channels, suggest a mechanism for channel opening similar to opening-closing of the iris in a camera diaphragm.
Serysheva
I I
II
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 USA.
Schatz
M
M
van Heel
M
M
Chiu
W
W
Hamilton
S L
SL
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D020285:Cryoelectron Microscopy; D004533:Egtazic Acid / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008024:Ligands; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D008024:Ligands; D019837:Ryanodine Receptor Calcium Release Channel; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium