Abstract
Calcium ATPase is a member of the P-type ATPases that transport ions across the membrane against a concentration gradient. Here we have solved the crystal structure of the calcium ATPase of skeletal muscle sarcoplasmic reticulum (SERCA1a) at 2.6 Å resolution with two calcium ions bound in the transmembrane domain, which comprises ten α-helices. The two calcium ions are located side by side and are surrounded by four transmembrane helices, two of which are unwound for efficient coordination geometry. The cytoplasmic region consists of three well separated domains, with the phosphorylation site in the central catalytic domain and the adenosine-binding site on another domain. The phosphorylation domain has the same fold as haloacid dehalogenase. Comparison with a low-resolution electron density map of the enzyme in the absence of calcium and with biochemical data suggests that large domain movements take place during active transport.
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Acknowledgements
We thank S. Adachi, N. Kamiya (Riken) and M. Kawamoto (JASRI) for their help in data taking at SPring-8, and K. Tani for computations. We acknowledge that very first crystals for X-ray were made by H. Mukai. This work was supported in part by grants-in-aid from the Ministry of Culture, Education, Science and Sports of Japan and from CRESTO (to C.T. and M.N.) and also by Toray Science Foundation (C.T.). This paper is dedicated to S. Ebashi, a founder of Ca2+-ATPase field and the father of the calcium theory.
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Toyoshima, C., Nakasako, M., Nomura, H. et al. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405, 647–655 (2000). https://doi.org/10.1038/35015017
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DOI: https://doi.org/10.1038/35015017
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