气候变化领域集成服务门户(CCPortal): Revealing atomic-scale molecular diffusion of a plant-transcription factor WRKY domain protein along DNA

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DOI	10.1073/pnas.2102621118
	Revealing atomic-scale molecular diffusion of a plant-transcription factor WRKY domain protein along DNA
	Dai L.; Xu Y.; Du Z.; Su X.-D.; Yu J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:23
英文摘要	Transcription factor (TF) target search on genome is highly essential for gene expression and regulation. High-resolution determination of TF diffusion along DNA remains technically challenging. Here, we constructed a TF model system using the plant WRKY domain protein in complex with DNA from crystallography and demonstrated microsecond diffusion dynamics of WRKY on DNA by employing all-atom molecular-dynamics (MD) simulations. Notably, we found that WRKY preferentially binds to one strand of DNA with significant energetic bias compared with the other, or nonpreferred strand. The preferential DNA-strand binding becomes most prominent in the static process, from nonspecific to specific DNA binding, but less distinct during diffusive movements of the domain protein on the DNA. Remarkably, without employing acceleration forces or bias, we captured a complete one-base-pair stepping cycle of the protein tracking along major groove of DNA with a homogeneous poly-adenosine sequence, as individual hydrogen bonds break and reform at the protein-DNA binding interface. Further DNA-groove tracking motions of the protein forward or backward, with occasional sliding as well as strand crossing to minor groove of DNA, were also captured. The processive diffusion of WRKY along DNA has been further sampled via coarse-grained MD simulations. The study thus provides structural dynamics details on diffusion of a small TF domain protein, suggests how the protein approaches a specific recognition site on DNA, and supports further high-precision experimental detection. The stochastic movements revealed in the TF diffusion also provide general clues about how other protein walkers step and slide along DNA. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Facilitated diffusion; Molecular dynamics; Specific recognition; Transcription factor; WRKY
语种	英语
scopus关键词	DNA; transcription factor; transcription factor WRKY; unclassified drug; Article; concentration (parameter); conformational transition; controlled study; crystal structure; crystallography; diffusion; DNA protein complex; DNA sequence; DNA strand; hydrogen bond; hydrophobicity; isothermal titration calorimetry; molecular dynamics; protein conformation; protein DNA binding
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238895
作者单位	Shenzhen JL Computational Science, Applied Research Institute, Shenzhen, 518131, China; Beijing Computational Science Research Center, Beijing, 100193, China; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, 100871, China; Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University, Beijing, 100871, China; Department of Physics and Astronomy, University of California, Irvine, CA 92697, United States; Department of Chemistry, University of California, Irvine, CA 92697, United States; NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, United States
推荐引用方式 GB/T 7714	Dai L.,Xu Y.,Du Z.,et al. Revealing atomic-scale molecular diffusion of a plant-transcription factor WRKY domain protein along DNA[J],2021,118(23).
APA	Dai L.,Xu Y.,Du Z.,Su X.-D.,&Yu J..(2021).Revealing atomic-scale molecular diffusion of a plant-transcription factor WRKY domain protein along DNA.Proceedings of the National Academy of Sciences of the United States of America,118(23).
MLA	Dai L.,et al."Revealing atomic-scale molecular diffusion of a plant-transcription factor WRKY domain protein along DNA".Proceedings of the National Academy of Sciences of the United States of America 118.23(2021).