Download MendeleyThe structural basis of calcium transport by the calcium pump.
Olesen, C., Picard, M., Winther, A.M., Gyrup, C., Morth, J.P., Oxvig, C., Moller, J.V., Nissen, P.(2007) Nature 450: 1036-1042
- PubMed: 18075584
- DOI: https://doi.org/10.1038/nature06418
- Primary Citation of Related Structures:
3B9B, 3B9R, 3BA6 - PubMed Abstract:
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.
Organizational Affiliation:
Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, University of Aarhus, Ole Worms Alle, blg. 1185, DK - 8000 Aarhus C, Denmark.
