title: Structural changes in the calcium pump accompanying the dissociation of calcium.
abstract: In skeletal muscle, calcium ions are transported (pumped) against a concentration gradient from the cytoplasm into the sarcoplasmic reticulum, an intracellular organelle. This causes muscle cells to relax after cytosolic calcium increases during excitation. The Ca(2+) ATPase that carries out this pumping is a representative P-type ion-transporting ATPase. Here we describe the structure of this ion pump at 3.1 A resolution in a Ca(2+)-free (E2) state, and compare it with that determined previously for the Ca(2+)-bound (E1Ca(2+)) state. The structure of the enzyme stabilized by thapsigargin, a potent inhibitor, shows large conformation differences from that in E1Ca(2+). Three cytoplasmic domains gather to form a single headpiece, and six of the ten transmembrane helices exhibit large-scale rearrangements. These rearrangements ensure the release of calcium ions into the lumen of sarcoplasmic reticulum and, on the cytoplasmic side, create a pathway for entry of new calcium ions.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan. ct@iam.u-tokyo.ac.jp
authors.forename: Chikashi
authors.initials: C
authors.lastname: Toyoshima
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nomura
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D019284:Thapsigargin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium