期刊論文
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 | en |
ISSN | 1520-5126 |
期刊性質 | 國外 |
收錄於 | SCI Scopus |
產學合作 | |
通訊作者 | |
審稿制度 | 否 |
國別 | USA |
公開徵稿 | |
出版型式 | ,電子版,紙本 |
相關連結 |
機構典藏連結 ( http://tkuir.lib.tku.edu.tw:8080/dspace/handle/987654321/122379 ) |