| Co-Investigator(Kenkyū-buntansha) |
OGAWA Haruo The University of Tokyo, Institute of Molecular and Cellular Biosciences, Research associate, 分子細胞生物学研究所, 助手 (40292726)
NAKASAKO Masayoshi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Lecturer, 分子細胞生物学研究所, 講師 (30227764)
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| Research Abstract |
The first goal of this research was to determine the atomic structure of the Ca^<2+>-ATPase of sarcoplasmic reticulum, a representative member of P-type ion translocating ATPases, using very thin 3D crystals of X-ray quality that we generated in the presence of calcium. The next goal was to crystallise the enzyme in other different physiological conditions. This research proceeded much faster than we had expected. We have already obtained atomic models for 3 different physiological states (ElCa^<2+>, E2 and E2P) and have succeeded in crystallising the enzyme in two other states (E1ATP and E1P analogues). The atomic models revealed structural changes accompanying the dissociation of Ca^<2+> and phosphate. That is, 6 out of 10 transmembrane α-helices undergo a large scale rearrangements and 3 cytoplasmic domains, which are widely separated with bound Ca^<2+>, gather to form a compact single headpiece when calcium ions dissociate. Two of the transmembrane helices show movements that contain large components normal to the membrane plane. These helices move like pistons on the binding and release of Ca^<2+> and the cytoplasmic domains serve as a energy converter that drives the pistons. Thus, our results indicate that P-type ion translocating ATPases have a mechanism like mechanical pumps at an atomic scale.
Some parts of these results were published in Nature in June 2000 and August 2002, and in PNAS in December 2002. These publications have collected considerable interests and been reviewed in detail in News and Views of Nature and Nature Structure Biology and in Editor's choice of Science. The results have been introduced already into world-standard text books of biochemistry and molecular biology.
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