Molecular dynamics simulation reveals DNA-specific recognition mechanism via c-Myb in pseudo-palindromic consensus of mim-1 promoter

文献类型： 外文期刊

第一作者： Weng, Jinru

作者： Weng, Jinru;Shen, Jinkang;Liu, Hongsen;Xu, Yuzi;Wang, Shan;Yang, Shuo;Hao, Dongyun

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关键词： c-Myb; DNA-specific recognition mechanism; Molecular dynamics simulation; DNA major groove width; Electrostatic potential; DNA(sic)(sic)(sic)(sic)(sic)(sic)(sic); (sic)offspring(sic)(sic)(sic)(sic)拟; DNA(sic)沟(sic)(sic); 静(sic)

期刊名称：JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B （ 影响因子：5.1； 五年影响因子：4.1 ）

ISSN： 1673-1581

年卷期： 2023 年 24 卷 10 期

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收录情况： SCI

摘要： This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (mim-1), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand (complex F) is more stable than that in the reverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.

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