2016 Fiscal Year Final Research Report
Structural biology of membrane transporters with a view to drug development
| Project/Area Number |
23000014
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Haruo 東京大学, 分子細胞生物学研究所, 准教授 (40292726)
MIMURA Hisatoshi 東京大学, 分子細胞生物学研究所, 助教 (30463904)
KANAI Ryuta 東京大学, 分子細胞生物学研究所, 助教 (50598472)
KABASHIMA Yoshiki 東京大学, 分子細胞生物学研究所, 助教 (00580573)
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| Research Collaborator |
Inesi Giuseppe カリフォルニアパシフィック医学センター研究所, 教授
Vilsen Bente オルフス大学, 教授
Cornelius Flemming オルフス大学, 教授
Karlish Steven ワイズマン研究所, 教授
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| Project Period (FY) |
2011 – 2016
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| Keywords | イオンポンプ / 膜蛋白質 / 結晶解析 / エネルギー変換 |
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| Outline of Final Research Achievements |
In this project, we aimed at complete understanding of the mechanism of active transport and pursued “why the structures of ion pumps have to be so” by carrying out crystal structure analyses of Ca^<2+>- and Na^+-pumps. With the Ca^<2+>-pump, we succeeded in elucidating the long-awaited E1 crystal structure and showed the regulatory mechanism of sarcolipin, an associated regulatory protein. With the Na^+ pump, we succeeded in determining the crystal structure of a Na^+-bound form for the first time, resulting in the elucidation of an intricate mechanism for selecting Na^+. We also determined the crystal structures of the Na^+-pump with various cardiotonic steroids and thereby opened a way towards developing a tissue specific compound. Furthermore, we succeeded in visualising lipid bilayers in the crystals of Ca^<2+>-ATPase in four states and described detailed interactions with phospholipids.
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