The Role of Charge Density Coupled DNA Bending in Transcription Factor Sequence Binding Specificity: A Generic Mechanism for Indirect Readout

doi:10.1021/jacs.1c11911

淡江大學機構典藏 > 理學院 > 化學學系暨研究所 > 期刊論文 > Item 987654321/122379

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/122379

题名:	The Role of Charge Density Coupled DNA Bending in Transcription Factor Sequence Binding Specificity: A Generic Mechanism for Indirect Readout
作者:	Chen, Xun;Tsai, Min-Yeh;Wolynes, Peter G.
日期:	2022-01-21
上传时间:	2022-03-04 12:16:11 (UTC+8)
出版者:	American Chemical Society
摘要:	The accurate reading of genetic information during transcription is essential for the expression of genes. Sequence binding specificity very often is attributed to short-range, usually specific interactions between amino acid residues and individual nucleotide bases through hydrogen bonding or hydrophobic contacts: “base readout” (direct readout). In contrast, many proteins recognize DNA sequences in an alternative fashion via “shape readout” (indirect readout), where many elements of the DNA sequence cooperate to localize the transcription factor. In this study, we use a coarse-grained protein–DNA model to investigate the origin of the sequence specificity of the protein PU.1 binding to its binding sites for a series of DNA sequences. We find that the binding specificity of PU.1 is achieved primarily via a nonspecific electrostatically driven DNA mechanism involving the change in the elastic properties of the DNA. To understand the underlying mechanism, we analyze how the mechanical properties of DNA change in relation to the location of the PU.1 bound along DNA. The simulations first show that electrostatic interactions between PU.1 and DNA can cause complex DNA conformational/dynamics changes. Using a semiflexible polymer theory, we find that PU.1 influences the DNA dynamics through a second-order mechanical effect. When PU.1 binds nonspecifically to the DNA via electrostatics, the DNA becomes stiffer and the protein slides along DNA in a search mode. In contrast, once the protein finds its specific binding site, the DNA becomes softer there. PU.1 thus locks into place through configurational entropy effects, which we suggest is a generic mechanism for indirect readout.
關聯:	Journal of the American Chemical Society 144(4), p.1835-1845
DOI:	10.1021/jacs.1c11911
显示于类别:	[化學學系暨研究所] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	67	检视/开启

在機構典藏中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....