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The structural basis of calcium transport by the calcium pump

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  • Claus Olesen
  • Martin Picard, Denmark
  • Anne-Marie Lund Winther, Denmark
  • Claus Gyrup Nielsen, Denmark
  • Jens Preben Morth, Denmark
  • Claus Oxvig
  • Jesper Vuust Møller, Denmark
  • Poul Nissen
  • Institute of Biophysics
  • Interdisciplinary Nanoscience Center
  • Department of Molecular Biology
The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, beryllium fluoride and aluminium fluoride, respectively. The structures complete the cycle of nucleotide binding and cation transport of Ca2+-ATPase. Phosphorylation of the enzyme triggers the onset of a conformational change that leads to the opening of a luminal exit pathway defined by the transmembrane segments M1 through M6, which represent the canonical membrane domain of P-type pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu 309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases are able to form the steep electrochemical gradients required for key functions in eukaryotic cells.
Original languageEnglish
Pages (from-to)1036-1042
Number of pages7
Publication statusPublished - 2007

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