Single Molecule Study of the Weak Biological Interactions Between P53 and DNA | |
Ying Yilun1; Zhang Xing1; Liu Yu1; Xue Mengzhu2; Li Honglin2,3; Long Yitao1 | |
刊名 | ACTA CHIMICA SINICA
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2013-01-15 | |
卷号 | 71期号:1页码:44-50 |
关键词 | nanopore alpha-hemolysin P53 weak interaction |
ISSN号 | 0567-7351 |
DOI | 10.6023/A12110982 |
文献子类 | Article |
英文摘要 | Many important cellular events, including protein-DNA interactions, are attributed to weak interactions. Almost all of the known biological functions of P53 depend critically upon its DNA-binding properties via numerous weak interactions. At the single-molecule level, information about the weak interactions between each residue of the P53 DNA binding domain (P53 DBD) and DNA is essential for understanding the biological function of P53 and for anti-cancer drug design. Here, we used the alpha-hemolysin (alpha-HL) pore to detect the weak interaction between a peptide of the P53 DBD (P53-P) and a 40-bp double-stranded DNA (B40) that includes the p21(wafl/cipl) DNA response element. The weak interactions in the complex of p53-P and B40 (p53-P:B40) produce a unique current trace through an alpha-HL nanopore with diagnostic ionic current blockages. Each current trace at a particular potential is related to the characterized behavior of captured p53-P:B40. Nanopore analysis indicates that the conformation of B40 might be changed by binding to p53-P, this change is confirmed by the molecule docking simulation. In the presence of the weak interactions between p53-P and B40, the analyte exhibits an increase in the rate constant of association with the nanopore vestibule. This reveals that the analyte-pore interactions could be enhanced by the weak interactions between p53-P and B40. The distorted B40 might be prone to translocate through the narrow constriction in the nanopore at the higher potential (> + 120 mV). Moreover, our findings demonstrate that the structure of distorted B40 in p53-P:B40 could be broken by the electric force. Our results support the possibility of identifying the weak interaction between two biomolecules. In addition, the analyte-pore association rate constant could be used to estimate the weak binding energy between different parts of the p53 binding domain and the target sequence. The signatures of the current trace may assist in the prediction of the conformational changes of biomolecules at the single-molecule level. Our observations suggest that a biological alpha-HL nanopore could be a candidate biosensor for predicting the conformational changes that result from weak interactions. |
资助项目 | Natural Science Foundation of China[91027035] ; Fundamental Research Funds for the Central Universities[WK1013002] ; Fundamental Research Funds for the Central Universities[WB1113005] ; National Science Fund for Distinguished Young Scholars of China[21125522] ; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning[00000000] |
WOS关键词 | ALPHA-HEMOLYSIN NANOPORE ; HAIRPIN MOLECULES ; PROTEIN PORE ; ION-CHANNEL ; BINDING ; POLYMERASE ; MUTATIONS ; PEPTIDES ; TRANSLOCATION ; RESOLUTION |
WOS研究方向 | Chemistry |
语种 | 中文 |
出版者 | SCIENCE PRESS |
WOS记录号 | WOS:000315605300005 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/277766] ![]() |
专题 | 药物发现与设计中心 |
通讯作者 | Ying Yilun |
作者单位 | 1.E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 3.Acad Sinica, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Ying Yilun,Zhang Xing,Liu Yu,et al. Single Molecule Study of the Weak Biological Interactions Between P53 and DNA[J]. ACTA CHIMICA SINICA,2013,71(1):44-50. |
APA | Ying Yilun,Zhang Xing,Liu Yu,Xue Mengzhu,Li Honglin,&Long Yitao.(2013).Single Molecule Study of the Weak Biological Interactions Between P53 and DNA.ACTA CHIMICA SINICA,71(1),44-50. |
MLA | Ying Yilun,et al."Single Molecule Study of the Weak Biological Interactions Between P53 and DNA".ACTA CHIMICA SINICA 71.1(2013):44-50. |
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