| アイテムタイプ |
共通アイテムタイプ(1) |
| 公開日 |
2025-02-06 |
| タイトル |
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|
タイトル |
Structures and mechanisms of actin ATP hydrolysis |
|
言語 |
en |
| 著者 |
Kanematsu, Yusuke
Narita, Akihiro
Oda, Toshiro
Koike, Ryotaro
Ota, Motonori
Takano, Yu
Moritsugu, Kei
Fujiwara, Ikuko
Tanaka, Kotaro
小松, 英幸
Nagae, Takayuki
Watanabe, Nobuhisa
Iwasa, Mitsusada
Maéda, Yuichiro
Takeda, Shuichi
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| 著作権関連情報 |
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|
権利情報 |
Copyright (c) 2022 the Author(s). Published by PNAS. |
| 著作権関連情報 |
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|
権利情報Resource |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
|
権利情報 |
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) PG–O3B bond cleavage; 3) four concomitant events: W1–PO3− formation, OH− and proton cleavage, nucleophilic attack by the OH− against PG, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi–bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes. |
|
言語 |
en |
| 書誌情報 |
en : Proceedings of the National Academy of Sciences of the United States of America
巻 119,
号 43,
発行日 2022-10-17
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| 出版社 |
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出版者 |
National Academy of Sciences |
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言語 |
en |
| キーワード |
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主題Scheme |
Other |
|
主題 |
actin |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
ATP hydrolysis |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
protein crystallography |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
QM/MM simulation |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| DOI |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1073/pnas.2122641119 |
| ISSN |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
0027-8424 |
| ISSN |
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収録物識別子タイプ |
EISSN |
|
収録物識別子 |
1091-6490 |
| 研究者情報 |
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|
URL |
https://hyokadb02.jimu.kyutech.ac.jp/html/284_ja.html |
| 論文ID（連携） |
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|
値 |
10445592 |
| 連携ID |
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|
値 |
12886 |
10445592.pdf (2.6 MB)
