中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 武汉物理与数学研究所
  3. 中国科学院武汉物理与数学研究所
Characterization of the interaction interface and conformational dynamics of human TGIF1 homeodomain upon the binding of consensus DNA

文献类型：期刊论文

作者Li, Shuangli1,3; Hu, Rui3; Yao, Haijie4; Long, Dong2,4; Luo, Fan3; Zhou, Xin3; Zhang, Xu3; Liu, Maili3; Zhu, Jiang3; Yang, Yunhuang3
刊名BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
出版日期2018-10-01
卷号1866期号:10页码:1021-1028
ISSN号1570-9639
关键词TG interacting factor-1 DNA recognition Interaction interface Conformational dynamics NMR spectroscopy
DOI10.1016/j.bbapap.2018.07.005
英文摘要The TG interacting factor-1 homeodomain (TGIF1-HD) binds with the consensus DNA motif 5'-TGTCA-3' in gene promoters through its three-amino acid loop extension (TALE) type homeodomain, and then recruits co-regulators to regulate gene expression. Although the solution NMR structure of human TGIF1-HD has been reported previously, little is known about its DNA binding mechanism. NMR titration have been extensively used to study mechanisms of ligand binding to target proteins; however, an intermediate exchange occurred predominantly between TGIF1-HD in the free and bound states when titrated with the consensus DNA, which resulted in poor-quality NMR spectra and precluded further exploration of its interaction interface and conformational dynamics. Here, the helix alpha 3 of TGIF1-HD was speculated as the specific DNA binding interface by hydrogen-deuterium exchange mass spectrometry (HDX-MS) experiments, and subsequently confirmed by chemical exchange saturation transfer (CEST) spectroscopy. In addition, simultaneous conformational changes in other regions, including alpha 1 and alpha 2, were induced by DNA binding, explaining the observation of chemical shift perturbations from extensive residues besides those located in alpha 3. Further, low-populated DNA-bound TGIF1-HD undergoing a slow exchange at a rate of 130.2 +/- 3.6 s(-1) was derived from the analysis of the CEST data, and two residues, R220 and R221, located in the middle of alpha 3 were identified to be crucial for DNA binding. Our study provides structural and dynamic insights into the mechanisms of TGIF1-HD recognition of extensive promoter DNA.
WOS关键词SMAD TRANSCRIPTIONAL COREPRESSOR ; NMR-SPECTROSCOPY ; PROTEIN ; MUTATIONS ; GENE ; REPRESSOR ; CARCINOMA ; EXCHANGE ; DOMAIN ; STATES
资助项目National Key R&D Program of China[2016YFA051201] ; National Natural Sciences Foundation of China[21575155] ; National Natural Sciences Foundation of China[21735007] ; Chinese Academy of Sciences[QYZDJ-SSW-SLH027]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
出版者ELSEVIER SCIENCE BV
WOS记录号WOS:000444662800003
资助机构National Key R&D Program of China ; National Key R&D Program of China ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China ; Chinese Academy of Sciences ; Chinese Academy of Sciences
源URL[http://ir.wipm.ac.cn/handle/112942/13102]  
专题中国科学院武汉物理与数学研究所
通讯作者Zhu, Jiang; Yang, Yunhuang
作者单位1.Grad Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
3.Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan 430071, Hubei, Peoples R China
4.Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Li, Shuangli,Hu, Rui,Yao, Haijie,et al. Characterization of the interaction interface and conformational dynamics of human TGIF1 homeodomain upon the binding of consensus DNA[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2018,1866(10):1021-1028.
APA Li, Shuangli.,Hu, Rui.,Yao, Haijie.,Long, Dong.,Luo, Fan.,...&Yang, Yunhuang.(2018).Characterization of the interaction interface and conformational dynamics of human TGIF1 homeodomain upon the binding of consensus DNA.BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,1866(10),1021-1028.
MLA Li, Shuangli,et al."Characterization of the interaction interface and conformational dynamics of human TGIF1 homeodomain upon the binding of consensus DNA".BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1866.10(2018):1021-1028.

入库方式： OAI收割

来源：武汉物理与数学研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。