检索结果-南通市图书馆

Structural and dynamic properties of the YTH domain in complex with N^(6)-methyladenosine RNA studied by accelerated molecular dynamics simulations

引用

Quantitative Biology 2023年第1期11卷 72-81页

作者： Mingwei Li Guanglin Chen Zhiyong Zhang MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics National Science Center for Physical Sciences at MicroscaleDivision of Life Sciences and Medicineand Biomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230026China Department of Physics University of Science and Technology of ChinaHefei 230026China

Background:N^(6)-methyladenosine(m^(6)A)modifications of mRNA and long non-coding RNA(lncRNAs)are known to play a significant role in regulation of gene expression and organismal development.Besides writer and eraser proteins of this dynamic modification,the YT521-B homology(YTH)domain can recognize the modification involved in numerous cellular processes.The function of proteins containing YTH domain and its binding mode with N^(6)-methyladenosine RNA has attracted considerable attention.However,the structural and dynamic characteristics of the YTH domain in complex with m^(6)A RNA is still unknown.Method:This work presents results of accelerated molecular dynamics(aMD)simulations at the timescale of microseconds.Principal component analysis(pca),molecular mechanics generalized Born surface area(MM/GBSA)calculations,contact analysis and contact-based principal component analysis(conpca)provide new insights into structure and dynamics of the YTH-RNA complex.Results:The aMD simulations indicate that the recognition loop has a larger movement away from the binding pocket in the YTH-A3 RNA than that in the YTH-m^(6)A3 RNA.In aMD trajectories of the apo YTH,there is a significant close-open transition of the recognition loop,that is to say,the apo YTH can take both the closed and open structure.We have found that the YTH domain binds more favorably to the methylated RNA than the nonmethylated RNA.The per-residue free energy decomposition and conpca suggest that hydrophobic residues including W380,L383-V385,W431-P434,M437,and M441-L442,may play important roles in favorable binding of the m^(6)A RNA to the YTH domain,which is also supported by aMD simulations of a double mutated system(L383A/M437A).Conclusion:The results are in good agreement with higher structural stability of the YTH-m^(6)A RNA than that of the YTH-A3 RNA.The addition of a methylation group on A3 can enhance its binding to the hydrophobic pocket in the YTH domain.Our simulations support a‘conformational selection’mechanism between the YTH-RNA binding

关键词： RNA methylation YTH-m^(6)A3 RNA principal component analysis(pca) binding free energy contactbased pca

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：