Molecular basis for PHF7-mediated ubiquitination of histone H3
- Hyun Sik Lee1,6,
- Injin Bang2,6,
- Junghyun You1,5,
- Tae-Kyeong Jeong3,
- Chang Rok Kim4,5,
- Minsang Hwang1,
- Jong-Seo Kim1,
- Sung Hee Baek4,
- Ji-Joon Song3 and
- Hee-Jung Choi1
- 1Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea;
- 2Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, New York 10016, USA;
- 3Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea;
- 4Creative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, Seoul 08826, South Korea
- Corresponding author: choihj{at}snu.ac.kr
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↵6 These authors contributed equally to this work.
Abstract
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.
Keywords
- E2 ubiquitin-conjugating enzyme
- plant homeodomain (PHD)
- plant homeodomain finger protein 7 (PHF7)
- RING E3 ubiquitin ligase
- histone H3
- structure
- ubiquitination
Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.350989.123.
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Freely available online through the Genes & Development Open Access option.
- Received July 24, 2023.
- Accepted November 6, 2023.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.