教師資料查詢 | 類別: 期刊論文 | 教師: 蔡旻燁MIN-YEH TSAI (瀏覽個人網頁)

標題:The Role of Charge Density Coupled DNA Bending in Transcription Factor Sequence Binding Specificity: A Generic Mechanism for Indirect Readout
學年110
學期1
出版(發表)日期2022/01/21
作品名稱The Role of Charge Density Coupled DNA Bending in Transcription Factor Sequence Binding Specificity: A Generic Mechanism for Indirect Readout
作品名稱(其他語言)
著者Xun Chen; Min-Yeh Tsai; Peter G. Wolynes
單位
出版者
著錄名稱、卷期、頁數Journal of the American Chemical Society 144(4), p.1835-1845
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.
關鍵字
語言英文
ISSN1520-5126
期刊性質國外
收錄於SCI;Scopus;
產學合作
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審稿制度
國別美國
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