hree-dimensional Structure of Nrf2-Maf transcription factor complex mediating the induction of phase II detoxifying enzymes

Nrf2-Maf转录因子复合物的三维结构介导II相解毒酶的诱导

• 批准号: 21510066
• 负责人: KUROKAWA Hirofumi
• 金额: $ 3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21510066/
• 关键词: タンパク質; 結晶構造解析; 毒性化学物質; 酸化ストレス; Keap1; Keapl

Nrf2 and Maf transcription factors form hetero dimmer and mediate the induction of phase II detoxifying enzymes in response to oxidative stress. We determined the crystal structure of Maf dimmer in complex with its cognate DNA and revealed the unique DNA recognition mechanism by Maf. We also determined the 3D structure of Keap1, a negative regulator of Nrf2 transcription factor in response to oxidative stress, by using single particle electron microscopy. Keap1 consists of two large spheres connected by stem region. In addition we found that p62, a selective autophagy substrate, competitively binds to Keap1 and activates Nrf2. Crystal structure of p62-Keap1 complex has been solved and showed that p62 competitively binds to Nrf2 binding pocket of Keap1.

NRF2和MAF转录因子形成杂型变暗器，并介导了响应氧化应激的II期解毒酶的诱导。我们确定了MAF调光的晶体结构与其同源DNA复杂化，并通过MAF揭示了独特的DNA识别机制。我们还通过使用单个粒子电子显微镜确定了Keap1的3D结构，Keap1是NRF2转录因子的负调节剂，响应氧化应激。 KEAP1由两个由茎区域连接的大球体组成。此外，我们发现p62是一种选择性自噬底物，竞争性地结合了KEAP1并激活NRF2。 P62-KEAP1复合物的晶体结构已解决，并表明p62竞争性地结合了KEAP1的NRF2结合袋。

项目成果

発癌性物質や酸化ストレスに応答する生体防御系センサーの構造基盤

响应致癌物和氧化应激的生物防御传感器的结构基础

• 发表时间: 2010
• 作者: 黒河博文;本橋ほづみ;佐藤主税;山本雅之
• 通讯作者: 山本雅之

酸化ストレスセンサー分子KEAP1阻害剤

氧化应激传感器分子KEAP1抑制剂

• 发表时间: 2011
• 期刊: 血管医学
• 作者: 黒河博文;山本雅之
• 通讯作者: 山本雅之

Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains

• DOI: 10.1073/pnas.0914036107
• 发表时间: 2010-02-16
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Ogura, Toshihiko;Tong, Kit I.;Yamamoto, Masayuki
• 通讯作者: Yamamoto, Masayuki

Structural Basis of Alternative DNA Recognition by Maf Transcription Factors

• DOI: 10.1128/mcb.00708-09
• 发表时间: 2009-12-01
• 期刊: MOLECULAR AND CELLULAR BIOLOGY
• 影响因子: 5.3
• 作者: Kurokawa, Hirofumi;Motohashi, Hozumi;Tanaka, Toshiyuki
• 通讯作者: Tanaka, Toshiyuki

The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1

• DOI: 10.1038/ncb2021
• 发表时间: 2010-03-01
• 期刊: NATURE CELL BIOLOGY
• 影响因子: 21.3
• 作者: Komatsu, Masaaki;Kurokawa, Hirofumi;Yamamoto, Masayuki
• 通讯作者: Yamamoto, Masayuki