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タイトル: | Inward- and outward-facing X-ray crystal structures of homodimeric P-glycoprotein CmABCB1 |
著者: | Kodan, Atsushi https://orcid.org/0000-0003-0317-9109 (unconfirmed) Yamaguchi, Tomohiro Nakatsu, Toru https://orcid.org/0000-0002-9582-4023 (unconfirmed) Matsuoka, Keita Kimura, Yasuhisa Ueda, Kazumitsu https://orcid.org/0000-0003-2980-6078 (unconfirmed) Kato, Hiroaki https://orcid.org/0000-0002-5993-4532 (unconfirmed) |
著者名の別形: | 小段, 篤史 山口, 知宏 中津, 亨 松岡, 敬太 木村, 泰久 植田, 和光 加藤, 博章 |
キーワード: | Transporters X-ray crystallography |
発行日: | 8-Jan-2019 |
出版者: | Springer Nature |
誌名: | Nature Communications |
巻: | 10 |
論文番号: | 88 |
抄録: | P-glycoprotein extrudes a large variety of xenobiotics from the cell, thereby protecting tissues from their toxic effects. The machinery underlying unidirectional multidrug pumping remains unknown, largely due to the lack of high-resolution structural information regarding the alternate conformational states of the molecule. Here we report a pair of structures of homodimeric P-glycoprotein: an outward-facing conformational state with bound nucleotide and an inward-facing apo state, at resolutions of 1.9 Å and 3.0 Å, respectively. Features that can be clearly visualized at this high resolution include ATP binding with octahedral coordination of Mg2+; an inner chamber that significantly changes in volume with the aid of tight connections among transmembrane helices (TM) 1, 3, and 6; a glutamate−arginine interaction that stabilizes the outward-facing conformation; and extensive interactions between TM1 and TM3, a property that distinguishes multidrug transporters from floppases. These structural elements are proposed to participate in the mechanism of the transporter. |
記述: | 多剤排出ポンプが薬を輸送するメカニズムを解明 --世界初の結晶構造が示すどんな薬でも絞り出す仕組み--. 京都大学プレスリリース. 2019-01-10. |
著作権等: | © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
URI: | http://hdl.handle.net/2433/236008 |
DOI(出版社版): | 10.1038/s41467-018-08007-x |
PubMed ID: | 30622258 |
関連リンク: | http://www.kyoto-u.ac.jp/ja/research/research_results/2018/190108_2.html |
出現コレクション: | 学術雑誌掲載論文等 |
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