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On-line Access: 2023-06-26
Received: 2022-12-07
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Jinru WENG, Shuo YANG, Jinkang SHEN, Hongsen LIU, Yuzi XU, Dongyun HAO, Shan WANG. Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of mim-1 promoter[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200634 @article{title="Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of mim-1 promoter", %0 Journal Article TY - JOUR
通过分子动力学模拟方法研究c-Myb在mim-1启动子区域伪回文序列的结合特性揭示DNA特异性识别机制1浙江大学医学院附属口腔医院,浙江大学口腔医学院,浙江省口腔疾病临床医学研究中心,浙江省口腔生物医学研究重点实验室,浙江大学癌症研究院,口腔生物材料与器械浙江省工程研究中心,中国杭州市,310000 2吉林大学分子酶学与工程教育部重点实验室,中国长春市,130021 3吉林省农业科学院农业生物技术研究所,中国长春市,130033 摘要:本研究旨在探索c-Myb转录因子在调控细胞早期分化和增殖过程中的DNA特异性识别机制。我们以鸡髓系基因mim-1为研究对象,研究其潜在双c-Myb结合位点的结合特异性。mim-1的c-Myb结合位点是一个伪回文序列AACGGTT,正反方向分别包含1个c-Myb结合保守序列AACNG。不同条件下的重复分子动力学模拟研究表明,c-Myb与mim-1正链的结合(复合物F)比与反链的结合(复合物R)更稳定。主成分分析(PCA)动力学轨迹分析表明,在330 K温度下,c-Myb识别螺旋R2和R3(R2R3)的开放运动导致复合物R中DNA与c-Myb解离,且此开放运动是由R2R3表面静电势降低引起。同时,DNA构象和氢键相互作用分析表明,复合物R中DNA的大沟宽度增加影响了R2R3与DNA间的氢键形成,直接导致DNA与R2R3的解离。拉伸分子动力学模拟研究进一步表明,静电势、DNA大沟宽度和氢键对DNA特异性识别起到重要作用。体外实验证实了计算模拟结果,即c-Myb只与mim-1正链结合。本研究表明,除一维保守序列AACNG外,三维结构特性对c-Myb的DNA特异性识别也起着重要作用。本研究结果有助于理解c-Myb在细胞早期分化和增殖中的调控机制,以及预测开发由c-Myb结合位点增多引起的肿瘤发生标志物。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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