CLC number: R725.8
On-line Access: 2020-11-05
Received: 2020-06-22
Revision Accepted: 2020-08-16
Crosschecked: 2020-10-13
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Ting Chen, Fan Tong, Xiao-yu Wu, Ling Zhu, Qiu-zi Yi, Jing Zheng, Ru-lai Yang, Zheng-yan Zhao, Xiao-hui Cang, Qiang Shu, Ping-ping Jiang. Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2000339 @article{title="Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency", %0 Journal Article TY - JOUR
极长链酰基辅酶A脱氢酶缺乏症ACADVL基因新发突变导致线粒体功能障碍创新点:本文从分子功能和结构的角度阐述6个新位点对蛋白和细胞功能的不同影响. 方法:通过体外构建突变载体建立各突变的过表达细胞系,检测各细胞系脂肪酸代谢能力、线粒体呼吸链功能、线粒体产三磷酸腺苷(ATP)能力、活性氧(ROS)和凋亡水平.同时检测了新发突变对蛋白二聚体稳定性的影响并用分子动力学模拟了突变蛋白构像的改变. 结论:突变(c.541C>T、c.863T>G、c.895A>G、c.1238T>C、c.1276G>A和c.1505T>A)过表达细胞系均表现出脂肪酸代谢障碍,线粒体呼吸链功能障碍,ATP产生水平下降和线粒体ROS水平上升.在无糖条件下,各细胞系的凋亡水平上升.各突变影响了极长链酰基辅酶A脱氢酶(VLCAD)蛋白二聚体的稳定性,分子动力学模拟预测每个突变均会导致VLCAD蛋白结构的发生重要构象变化. 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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[41]List of electronic supplementary materials [42]Fig. S1 Variants in VLCAD-deficient patients and their conservation of residues [43]Fig. S2 Expression levels of HA-tagged VLCAD in cells [44]Fig. S3 FAO capacity for utilization of exogenous palmitate [45]Fig. S4 Structural predictions in wild-type and mutant residues Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou
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