EMD-23806
Structure of yeast Ubr1 in complex with Ubc2 and N-degron
EMD-23806
Single-particle3.35 Å
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Map released: 24/11/2021
Last modified: 29/05/2024
Sample Organism:
Saccharomyces cerevisiae (strain ATCC 204508 / S288c),
Homo sapiens
Sample: yeast Ubr1 in complex with Ubc2 and N-degron
Fitted models: 7mex (Avg. Q-score: 0.45)
Raw data: EMPIAR-10886
Deposition Authors: Pan M
,
Zheng Q
Sample: yeast Ubr1 in complex with Ubc2 and N-degron
Fitted models: 7mex (Avg. Q-score: 0.45)
Raw data: EMPIAR-10886
Deposition Authors: Pan M
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Structural insights into Ubr1-mediated N-degron polyubiquitination.
Pan M
,
Zheng Q,
Wang T
,
Liang L,
Mao J,
Zuo C
,
Ding R
,
Ai H,
Xie Y
,
Si D
,
Yu Y
,
Liu L
,
Zhao M
(2021) Nature , 600 , 334 - 338
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(2021) Nature , 600 , 334 - 338
Abstract:
The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation1. In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N-degron pathway2. 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.
The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation1. In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N-degron pathway2. 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.