phf7介导组蛋白H3泛素化的分子基础。

IF 7.5 1区 生物学 Q1 CELL BIOLOGY Genes & development Pub Date : 2023-12-26 DOI:10.1101/gad.350989.123
Hyun Sik Lee, Injin Bang, Junghyun You, Tae-Kyeong Jeong, Chang Rok Kim, Minsang Hwang, Jong-Seo Kim, Sung Hee Baek, Ji-Joon Song, Hee-Jung Choi
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引用次数: 0

摘要

环型E3连接酶已被发现超过二十年,但其多种作用模式仍然是活跃研究的主题。Plant homeodomain (PHD) finger protein 7 (PHF7)是一种参与组蛋白泛素化的环型E3泛素连接酶。PHF7包含三个锌指结构域:扩展PHD (ePHD)、RING结构域和PHD。虽然RING结构域的功能在很大程度上被理解,但其他两个结构域在E3连接酶活性中的作用仍然难以捉摸。在这里,我们展示了PHF7与E2泛素结合酶(E2)配合物的晶体结构。我们的结构表明,E2在RING结构域和c端PHD之间被有效捕获,促进了E2通过直接接触募集。此外,通过体外结合和功能分析,我们证明n端epd通过DNA结合识别核小体,而c端PHD参与组蛋白H3识别。我们的研究结果为PHF7的E3连接酶活性提供了分子基础,并揭示了每个结构域对PHF7泛素化活性的具体而协同的贡献。
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Molecular basis for PHF7-mediated ubiquitination of histone H3.

The RING-type E3 ligase has been known for over two decades, yet its diverse modes of action are still the subject of active research. Plant homeodomain (PHD) finger protein 7 (PHF7) is a RING-type E3 ubiquitin ligase responsible for histone ubiquitination. PHF7 comprises three zinc finger domains: an extended PHD (ePHD), a RING domain, and a PHD. While the function of the RING domain is largely understood, the roles of the other two domains in E3 ligase activity remain elusive. Here, we present the crystal structure of PHF7 in complex with the E2 ubiquitin-conjugating enzyme (E2). Our structure shows that E2 is effectively captured between the RING domain and the C-terminal PHD, facilitating E2 recruitment through direct contact. In addition, through in vitro binding and functional assays, we demonstrate that the N-terminal ePHD recognizes the nucleosome via DNA binding, whereas the C-terminal PHD is involved in histone H3 recognition. Our results provide a molecular basis for the E3 ligase activity of PHF7 and uncover the specific yet collaborative contributions of each domain to the PHF7 ubiquitination activity.

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来源期刊
Genes & development
Genes & development 生物-发育生物学
CiteScore
17.50
自引率
1.90%
发文量
71
审稿时长
3-6 weeks
期刊介绍: Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers. Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).
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