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タイトル: Outward open conformation of a Major Facilitator Superfamily multidrug/H⁺ antiporter provides insights into switching mechanism
著者: Nagarathinam, Kumar
Nakada-Nakura, Yoshiko
Parthier, Christoph
Terada, Tohru
Juge, Narinobu
Jaenecke, Frank
Liu, Kehong
Hotta, Yunhon
Miyaji, Takaaki
Omote, Hiroshi
Iwata, So
Nomura, Norimichi  kyouindb  KAKEN_id
Stubbs, Milton T.
Tanabe, Mikio
著者名の別形: 名倉, 淑子
寺田, 透
樹下, 成信
宮地, 孝明
表, 弘志
岩田, 想
野村, 紀通
田辺, 幹雄
発行日: 1-Oct-2018
出版者: Springer Nature America, Inc
誌名: Nature Communications
巻: 9
論文番号: 4005
抄録: Multidrug resistance (MDR) poses a major challenge to medicine. A principle cause of MDR is through active efflux by MDR transporters situated in the bacterial membrane. Here we present the crystal structure of the major facilitator superfamily (MFS) drug/H⁺ antiporter MdfA from Escherichia coli in an outward open conformation. Comparison with the inward facing (drug binding) state shows that, in addition to the expected change in relative orientations of the N- and C-terminal lobes of the antiporter, the conformation of TM5 is kinked and twisted. In vitro reconstitution experiments demonstrate the importance of selected residues for transport and molecular dynamics simulations are used to gain insights into antiporter switching. With the availability of structures of alternative conformational states, we anticipate that MdfA will serve as a model system for understanding drug efflux in MFS MDR antiporters.
記述: 薬剤耐性の原因「薬剤汲み出しタンパク質」の排出メカニズムを解明 --多剤排出トランスポーターMdfAの分子機構-- 京都大学プレスリリース. 2018-10-03.
著作権等: © The Author(s) 2018
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/2433/234663
DOI(出版社版): 10.1038/s41467-018-06306-x
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/181001_2.html
出現コレクション:学術雑誌掲載論文等

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