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-Structure paper
タイトル | Structure of the human UBR5 E3 ubiquitin ligase. |
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ジャーナル・号・ページ | Structure, Vol. 31, Issue 5, Page 541-552.e4, Year 2023 |
掲載日 | 2023年5月4日 |
著者 | Feng Wang / Qing He / Wenhu Zhan / Ziqi Yu / Efrat Finkin-Groner / Xiaojing Ma / Gang Lin / Huilin Li / |
PubMed 要旨 | The human UBR5 is a single polypeptide chain homology to E6AP C terminus (HECT)-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions like an ...The human UBR5 is a single polypeptide chain homology to E6AP C terminus (HECT)-type E3 ubiquitin ligase essential for embryonic development in mammals. Dysregulated UBR5 functions like an oncoprotein to promote cancer growth and metastasis. Here, we report that UBR5 assembles into a dimer and a tetramer. Our cryoelectron microscopy (cryo-EM) structures reveal that two crescent-shaped UBR5 monomers assemble head to tail to form the dimer, and two dimers bind face to face to form the cage-like tetramer with all four catalytic HECT domains facing the central cavity. Importantly, the N-terminal region of one subunit and the HECT of the other form an "intermolecular jaw" in the dimer. We show the jaw-lining residues are important for function, suggesting that the intermolecular jaw functions to recruit ubiquitin-loaded E2 to UBR5. Further work is needed to understand how oligomerization regulates UBR5 ligase activity. This work provides a framework for structure-based anticancer drug development and contributes to a growing appreciation of E3 ligase diversity. |
リンク | Structure / PubMed:37040767 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.66 - 3.5 Å |
構造データ | EMDB-27201: EM map of the human UBR5 HECT-type E3 ubiquitin ligase in a dimeric form EMDB-27822: EM map of the human UBR5 HECT-type E3 ubiquitin ligase in a C2 symmetric dimeric form EMDB-28646: EM map of the human UBR5 HECT-type E3 ubiquitin ligase in a tetrameric form |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | LIGASE / HECT / E3 ligase / Dimer |