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论文题目: gamma-Secretase Modulators and Inhibitors Induce Different Conformational Changes of Presenilin 1 Revealed by FLIM and FRET
英文论文题目: gamma-Secretase Modulators and Inhibitors Induce Different Conformational Changes of Presenilin 1 Revealed by FLIM and FRET
第一作者: Wang, X; Cui, J; Li, W; Zeng, XL; Zhao, J; Pei, G
英文第一作者: Wang, X; Cui, J; Li, W; Zeng, XL; Zhao, J; Pei, G
联系作者: Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2015
卷: 47
期: 4
页码: 927-937
摘要: Elucidation of gamma-secretase structure and dynamic conformational changes is of importance to drug discovery targeting this enzyme. Electron microscopy analyses provided important structural information, but the dynamic changes of gamma-secretase in cells need to be explored further. We found that PS1 internal fluorescence resonance energy transfer (FRET) probes can incorporate into gamma-secretase complex and possess secretase activity. Our results from fluorescence lifetime image microscopy (FLIM) and acceptor photobleaching FRET show different PS1 internal FRET when PS1 fluorescent probes expressed alone or with other secretase subunits Aph1aL, Nicastrin, and Pen2, indicating that PS1 internal FRET could be applied for probing conformational change of gamma-secretase complex. Further, we accessed whether gamma-secretase activity interfering compounds induced different conformational changes of PS1. Our results show that both gamma-secretase modulators and inhibitors affect PS1 internal FRET but in different manners. These results demonstrate that FLIM and acceptor photobleaching FRET could be applied to monitor different PS1 conformational changes in gamma-secretase.
英文摘要: Elucidation of gamma-secretase structure and dynamic conformational changes is of importance to drug discovery targeting this enzyme. Electron microscopy analyses provided important structural information, but the dynamic changes of gamma-secretase in cells need to be explored further. We found that PS1 internal fluorescence resonance energy transfer (FRET) probes can incorporate into gamma-secretase complex and possess secretase activity. Our results from fluorescence lifetime image microscopy (FLIM) and acceptor photobleaching FRET show different PS1 internal FRET when PS1 fluorescent probes expressed alone or with other secretase subunits Aph1aL, Nicastrin, and Pen2, indicating that PS1 internal FRET could be applied for probing conformational change of gamma-secretase complex. Further, we accessed whether gamma-secretase activity interfering compounds induced different conformational changes of PS1. Our results show that both gamma-secretase modulators and inhibitors affect PS1 internal FRET but in different manners. These results demonstrate that FLIM and acceptor photobleaching FRET could be applied to monitor different PS1 conformational changes in gamma-secretase.
刊物名称: JOURNAL OF ALZHEIMERS DISEASE
英文刊物名称: JOURNAL OF ALZHEIMERS DISEASE
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学科: Neurosciences & Neurology
英文学科: Neurosciences & Neurology
影响因子: 4.151
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论文类别: Article
英文论文类别: Article
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