Structural basis for DNA recognition by STAT6
文献类型：期刊论文
| 作者 | Li, Jing8,9 ; Rodriguez, Jose Pindado5; Niu, Fengfeng8; Pu, Mengchen8; Wang, Jinan10; Hung, Li-Wei6; Shao, Qiang10; Zhu, Yanping8; Ding, Wei8; Liu, Yanqing8
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| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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| 出版日期 | 2016-11-15 |
| 卷号 | 113期号:46页码:13015-13020 |
| 关键词 | STAT6 N4 site DNA recognition JAK-STAT pathway antiviral innate immunity crystal structure |
| ISSN号 | 0027-8424 |
| DOI | 10.1073/pnas.1611228113 |
| 文献子类 | Article |
| 英文摘要 | STAT6 participates in classical IL-4/IL-13 signaling and stimulator of interferon genes-mediated antiviral innate immune responses. Aberrations in STAT6-mediated signaling are linked to development of asthma and diseases of the immune system. In addition, STAT6 remains constitutively active in multiple types of cancer. Therefore, targeting STAT6 is an attractive proposition for treating related diseases. Although a lot is known about the role of STAT6 in transcriptional regulation, molecular details on how STAT6 recognizes and binds specific segments of DNA to exert its function are not clearly understood. Here, we report the crystal structures of a homodimer of phosphorylated STAT6 core fragment (STAT6(CF)) alone and bound with the N3 and N4 DNA binding site. Analysis of the structures reveals that STAT6 undergoes a dramatic conformational change on DNA binding, which was further validated by performing molecular dynamics simulation studies and small angle X-ray scattering analysis. Our data show that a larger angle at the intersection where the two protomers of STAT meet and the presence of a unique residue, H415, in the DNA-binding domain play important roles in discrimination of the N4 site DNA from the N3 site by STAT6. H415N mutation of STAT6CF decreased affinity of the protein for the N4 site DNA, but increased its affinity for N3 site DNA, both in vitro and in vivo. Results of our structure-function studies on STAT6 shed light on mechanism of DNA recognition by STATs in general and explain the reasons underlying STAT6's preference for N4 site DNA over N3. |
| WOS关键词 | TRANSCRIPTIONAL ACTIVITY ; UNPHOSPHORYLATED STAT1 ; CRYSTAL-STRUCTURE ; SH2 DOMAIN ; BINDING ; DIMER ; REVEALS ; COMPLEX ; PROTEIN ; SITES |
| 资助项目 | National Natural Science Foundation of China[31570875] ; National Natural Science Foundation of China[31330019] ; National Natural Science Foundation of China[81590761] ; Ministry of Science and Technology of China[2014CB910400] ; Ministry of Science and Technology of China[2013CB911103] ; Beijing Nova Program[Z141102001814020] ; Youth Innovation Promotion Association Chinese Academy of Sciences[2013065] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000388970100052 |
| 出版者 | NATL ACAD SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275807]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Ouyang, Songying |
| 作者单位 | 1.Univ Oulu, Bioctr Oulu, SF-90220 Oulu, Finland; 2.Univ Oulu, Fac Biochem & Mol Med, SF-90220 Oulu, Finland; 3.Shanghai Tech Univ, iHuman Inst, Shanghai 201210, Peoples R China; 4.Kunming Med Univ, Inst Mol & Clin Med, Kunming 650500, Peoples R China 5.Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA; 6.Los Alamos Natl Lab, Phys Div, Los Alamos, NM 87545 USA; 7.Tianjin Med Univ, Dept Immunol, Tianjin 300070, Peoples R China; 8.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China; 9.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 10.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Jing,Rodriguez, Jose Pindado,Niu, Fengfeng,et al. Structural basis for DNA recognition by STAT6[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2016,113(46):13015-13020. |
| APA | Li, Jing.,Rodriguez, Jose Pindado.,Niu, Fengfeng.,Pu, Mengchen.,Wang, Jinan.,...&Ouyang, Songying.(2016).Structural basis for DNA recognition by STAT6.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,113(46),13015-13020. |
| MLA | Li, Jing,et al."Structural basis for DNA recognition by STAT6".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113.46(2016):13015-13020. |
入库方式： OAI收割
来源：上海药物研究所
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