| Item type |
学術雑誌論文 / Journal Article.(1) |
| 公開日 |
2021-03-09 |
| 書誌情報 |
en : JOURNAL OF BIOLOGICAL CHEMISTRY
巻 288,
号 3,
p. 1739-1749,
発行日 2013
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| タイトル |
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タイトル |
Rapid Nucleotide Exchange Renders Asp-11 Mutant Actins Resistant to Depolymerizing Activity of Cofilin, Leading to Dominant Toxicity in Vivo |
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言語 |
en |
| 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 |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 著者 |
UMEKI, Nobuhisa
NAKAJIMA, Jun
NOGUCHI, Taro Q. P.
徳樂, 清孝
NAGASAKI, Akira
ITO, Kohji
HIROSE, Keiko
UYEDA, Taro Q. P.
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| 室蘭工業大学研究者データベースへのリンク |
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表示名 |
徳樂 清孝（TOKURAKU Kiyotaka） |
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URL |
http://rdsoran.muroran-it.ac.jp/html/100000137_ja.html |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Conserved Asp-11 of actin is a part of the nucleotide binding pocket, and its mutation to Gln is dominant lethal in yeast, whereas the mutation to Asn in human alpha-actin dominantly causes congenital myopathy. To elucidate the molecular mechanism of those dominant negative effects, we prepared Dictyostelium versions of D11N and D11Q mutant actins and characterized them in vitro. D11N and D11Q actins underwent salt-dependent reversible polymerization, although the resultant polymerization products contained small anomalous structures in addition to filaments of normal appearance. Both monomeric and polymeric D11Q actin released bound nucleotides more rapidly than the wild type, and intriguingly, both monomeric and polymeric D11Q actins hardly bound cofilin. The deficiency in cofilin binding can be explained by rapid exchange of bound nucleotide with ATP in solution, because cofilin does not bind ATP-bound actin. Copolymers of D11Q and wild type actins bound cofilin, but cofilin-induced depolymerization of the copolymers was slower than that of wild type filaments, which may presumably be the primary reason why this mutant actin is dominantly toxic in vivo. Purified D11N actin was unstable, which made its quantitative biochemical characterization difficult. However, monomeric D11N actin released nucleotides even faster than D11Q, and we speculate that D11N actin also exerts its toxic effects in vivo through a defective interaction with cofilin. We have recently found that two other dominant negative actin mutants are also defective in cofilin binding, and we propose that the defective cofilin binder is a major class of dominant negative actin mutants. |
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言語 |
en |
| 出版者 |
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出版者 |
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
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言語 |
en |
| 出版者版へのリンク |
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表示名 |
10.1074/jbc.M112.404657 |
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URL |
https://doi.org/10.1074/jbc.M112.404657 |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.1074/jbc.M112.404657 |
| 日本十進分類法 |
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主題Scheme |
NDC |
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主題 |
499 |
| 権利 |
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言語 |
en |
|
権利情報 |
https://creativecommons.org/licenses/by/4.0/ |
| 著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
JOBC_288_3_1739_1749 (2.2 MB)
