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
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.
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).