Structural basis for the interaction of TAK1 kinase with its activating protein TAB1.

Brown K; Vial SC; Dedi N; Long JM; Dunster NJ; Cheetham GM

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Structural basis for the interaction of TAK1 kinase with its activating protein TAB1.

机译：TAK1激酶与其活化蛋白TAB1相互作用的结构基础。

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Transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK family of protein kinases, and is involved in intracellular signalling pathways stimulated by transforming growth factor beta, interleukin-1 and tumour necrosis factor-alpha. TAK1 is known to rely upon an additional protein, TAK1-binding protein 1 (TAB1), for complete activation. However, the molecular basis for this activation has yet to be elucidated. We have solved the crystal structure of a novel TAK1 chimeric protein and these data give insight into how TAK1 is activated by TAB1. Our results reveal a novel binding pocket on the TAK1 kinase domain whose shape complements that of a unique alpha-helix in the TAK1 binding domain of TAB1, providing the basis for an intimate hydrophobic association between the protein activator and its target.

机译：转化生长因子-β（TGF-beta）激活的激酶1（TAK1）是MAPKKK蛋白激酶家族的成员，并参与由转化生长因子β，白介素-1和肿瘤坏死因子-刺激的细胞内信号通路。 α。已知TAK1依赖于另一种蛋白TAK1结合蛋白1（TAB1）来完全激活。但是，这种激活的分子基础尚未阐明。我们已经解决了新型TAK1嵌合蛋白的晶体结构，并且这些数据提供了TAB1如何激活TAK1的见解。我们的结果揭示了TAK1激酶结构域上的新型结合口袋，其形状与TAB1的TAK1结合结构域中独特的α-螺旋的形状互补，为蛋白质激活剂与其靶标之间的紧密疏水缔合提供了基础。

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来源
《Journal of Molecular Biology》 |2005年第5期|共8页
作者
Brown K; Vial SC; Dedi N; Long JM; Dunster NJ; Cheetham GM;
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正文语种 eng
中图分类基础医学;
关键词
MAP Kinase Kinase Kinases;

机译：MAP激酶激酶激酶;

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专利

1. Structural basis for the interaction of TAK1 kinase with its activating protein TAB1. [J] . Brown K, Vial SC, Dedi N, Journal of Molecular Biology . 2005,第5期

机译：TAK1激酶与其活化蛋白TAB1相互作用的结构基础。
2. Discovery of Type II Inhibitors of TGF beta-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2) [J] . Tan Li, Nomanbhoy Tyzoon, Gurbani Deepak, Journal of Medicinal Chemistry . 2015,第1期

机译：发现TGFβ激活激酶1（TAK1）和丝裂原激活的蛋白激酶激酶激酶2（MAP4K2）的II型抑制剂。
3. Phosphorylation‐dependent activation of TAK1 mitogen‐activated protein kinase kinase kinase by TAB1 [J] . Miyoshi Hidetaka, Mizukami Junko, Sakurai Hiroaki, FEBS Letters . 2000,第2a3期

机译：TAB1的磷酸化依赖性激活TAK1丝裂原活化的蛋白激酶激酶
4. Structural Protein Interactions Predict Kinase-Inhibitor Interactions in Upregulated Pancreas Tumour Genes Expression Data [C] . Gihan Dawelbait, Christian Pilarsky, Yanju Zhang, International Symposium on Computational Life Sciences(CompLife 2005); 20050925-27; Konstanz(DE) . 2005

机译：结构蛋白相互作用预测上调胰腺肿瘤基因表达数据中的激酶抑制剂相互作用。
5. Molecular studies on the effects of phosphorylation by p21-activated protein kinase Pak2 on protein kinase activation and protein interactions. [D] . Jung, Jin-Hun. 2004

机译：p21激活的蛋白激酶Pak2磷酸化对蛋白激酶激活和蛋白相互作用的影响的分子研究。
6. Reciprocal Inhibition between the Transforming Growth Factor-β-activated Kinase 1 (TAK1) and Apoptosis Signal-regulating Kinase 1 (ASK1) Mitogen-activated Protein Kinase Kinase Kinases and Its Suppression by TAK1-binding Protein 2 (TAB2) an Adapter Protein for TAK1 [O] . So Yong Kim, Jea-Hyuck Shim, Eunyoung Chun, 2012

机译：转化生长因子-β激活的激酶1（TAK1）和凋亡信号调节激酶1（ASK1）的丝裂原激活的蛋白激酶激酶之间的相互抑制和抑制TAK1结合蛋白2（TAB2）的适配器蛋白。 TAK1
7. Transforming Growth Factor β-activated Kinase 1 (TAK1) Kinase Adaptor, TAK1-binding Protein 2, Plays Dual Roles in TAK1 Signaling by Recruiting Both an Activator and an Inhibitor of TAK1 Kinase in Tumor Necrosis Factor Signaling Pathway* [O] . Broglie, Peter, Matsumoto, Kunihiro, Akira, Shizuo, 2009

机译：转化生长因子β活化激酶1（TAK1）激酶适配器，TAK1结合蛋白2，通过在肿瘤坏死因子信号通路中募集TAK1激酶的激活剂和抑制剂，在TAK1信号中起双重作用*

Structural basis for the interaction of TAK1 kinase with its activating protein TAB1.

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