Activation mechanism of G protein-coupled receptors by X-ray free electron lasers
Project/Area Number |
18H02394
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 43020:Structural biochemistry-related
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Research Institution | Tohoku University (2020) Institute of Physical and Chemical Research (2018-2019) |
Principal Investigator |
Nango Eriko 東北大学, 多元物質科学研究所, 教授 (90376947)
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Co-Investigator(Kenkyū-buntansha) |
浅田 秀基 京都大学, 医学研究科, 特定講師 (20399041)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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Keywords | X線結晶構造解析 / Gタンパク質共役型受容体 / X線自由電子レーザー / シリアルフェムト秒結晶構造解析 / ロドプシン / X線自由電子レーザー |
Outline of Final Research Achievements |
We conducted this research to analyze dynamic structures of visual rhodopsin, which is one of G protein-coupled receptors, using X-ray free electron lasers (XFEL). So far, time-resolved crystallography using XFEL has enabled to visualize dynamic structures of several light-sensitive proteins. However, it has been challenging to measure visual rhodopsin crystals because the crystal is damaged by very weak light. It has been also challenging to obtain rhodopsin crystals diffracting with high spatial resolution. We developed a new experimental device for time-resolved serial femtosecond crystallography to transport samples discontinuously for less light contamination. We performed pump-probe type time-resolved experiments with photo-sensitive samples using the device and observed structural changes with time. In addition, various expression systems of visual rhodopsin have been examined, and crystals were obtained under several conditions.
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Academic Significance and Societal Importance of the Research Achievements |
従来、活性化状態に至る途中構造など動的構造を原子分解能で得ることは困難であった。新たな放射光源であるX線自由電子レーザー(XFEL)を用いると動的構造を可視化することが可能であるが、視覚ロドプシンのような取り扱いが難しい試料の測定に適した装置や技術は達成されていなかった。本課題ではXFEL実験用装置開発に取り組み、新たな測定方法を確立した。こうした技術は他試料の動的構造決定においても貢献すると期待される。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone2020
Author(s)
Im Dohyun、Inoue Asuka、Fujiwara Takaaki、Nakane Takanori、Yamanaka Yasuaki、Uemura Tomoko、Mori Chihiro、Shiimura Yuki、Kimura Kanako Terakado、Asada Hidetsugu、Nomura Norimichi、Tanaka Tomoyuki、Yamashita Ayumi、Nango Eriko、Tono Kensuke、Kadji Francois Marie Ngako、Aoki Junken、Iwata So、Shimamura Tatsuro
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 1-11
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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