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Structural changes in XRCC4 mutants mimicking phosphorylation
https://repo.qst.go.jp/records/83354
https://repo.qst.go.jp/records/83354d63e8e46-502a-43b6-b43c-dc8df2ae8640
Item type | 会議発表用資料 / Presentation(1) | |||||
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公開日 | 2021-09-17 | |||||
タイトル | ||||||
タイトル | Structural changes in XRCC4 mutants mimicking phosphorylation | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
資源タイプ | conference object | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
西久保, 開
× 西久保, 開× Kai, Nishikubo |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Phosphorylation regulates activation of proteins that repair DNA damage caused by ionizing radiation. XRCC4 is a key protein for the repair to form a multimeric scaffold that connects DNA and LigIV. It is known that at least five phosphorylation sites are localized to the C-terminal side. However, it is not clear how phosphorylation contributes to the regulation of XRCC4 activity. We hypothesized that a negative charge provided by phosphorylation alters the local static charge distribution of this molecule, causing its conformational changes and turning the activation switch on. In this study, the structural changes occurring in XRCC4 was investigated using circular dichroism (CD) spectroscopy. Analyzing obtained CD spectra revealed that proportion of α-helix in all secondary structures of the XRCC4 dimer or multimer was 45% or 38%, for β-strand 9% or 15%, respectively. Presumably, α-helix may interfere with the multimerization and β-strand may stabilize it by the hydrogen bonding. For further investigation of the structural change by phosphorylation, we prepared XRCC4 mutants with a substitution of a residue which are phosphorylated with an aspartic acid that provides similar negative charge distribution to that for wildtype protein. The mutant dimers showed similar structures. For the multimers, α-helix proportion in the mutants decreased by 5% and β-strand proportion increased by 5%, compared to that for wild type. The phosphorylation would facilitate the multimerization, stabilize the multimeric scaffold and promote the DNA repair process. | |||||
会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 日本放射線影響学会第64回大会 | |||||
発表年月日 | ||||||
日付 | 2021-09-22 | |||||
日付タイプ | Issued |