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Structure paper

タイトル	Structural insights into Ubr1-mediated N-degron polyubiquitination.
ジャーナル・号・ページ	Nature, Vol. 600, Issue 7888, Page 334-338, Year 2021
掲載日	2021年11月17日
著者	Man Pan / Qingyun Zheng / Tian Wang / Lujun Liang / Junxiong Mao / Chong Zuo / Ruichao Ding / Huasong Ai / Yuan Xie / Dong Si / Yuanyuan Yu / Lei Liu / Minglei Zhao /
PubMed 要旨	The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation. In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N- ...The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation. In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N-degron pathway. How Ubr1 mediates the initiation of ubiquitination and the elongation of the ubiquitin chain in a linkage-specific manner through a single E2 ubiquitin-conjugating enzyme (Ubc2) remains unknown. Here we developed chemical strategies to mimic the reaction intermediates of the first and second ubiquitin transfer steps, and determined the cryo-electron microscopy structures of Ubr1 in complex with Ubc2, ubiquitin and two N-degron peptides, representing the initiation and elongation steps of ubiquitination. Key structural elements, including a Ubc2-binding region and an acceptor ubiquitin-binding loop on Ubr1, were identified and characterized. These structures provide mechanistic insights into the initiation and elongation of ubiquitination catalysed by Ubr1.
リンク	Nature / PubMed:34789879 / PubMed Central
手法	EM (単粒子)
解像度	3.35 - 7.69 Å
構造データ	23806 7mex EMDB-23806, PDB-7mex: Structure of yeast Ubr1 in complex with Ubc2 and N-degron 手法: EM (単粒子) / 解像度: 3.35 Å 23807 7mey EMDB-23807, PDB-7mey: Structure of yeast Ubr1 in complex with Ubc2 and monoubiquitinated N-degron 手法: EM (単粒子) / 解像度: 3.67 Å EMDB-24935: CryoEM map of yeast Ubr1 in complex with monoubiquitinated N-degron 手法: EM (単粒子) / 解像度: 6.04 Å EMDB-24936: CryoEM map of yeast Ubr1 手法: EM (単粒子) / 解像度: 7.69 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-Z3V: 2-(ethylamino)ethane-1-thiol
由来	saccharomyces cerevisiae (strain atcc 204508 / s288c) (パン酵母) homo sapiens (ヒト) saccharomyces cerevisiae s288c (パン酵母) Saccharomyces cerevisiae (パン酵母)
キーワード	TRANSFERASE / Ubiquitin E3 ligase / ubiquitination / Ubr1 / Ubc2 / Degron / N-end rule