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-Structure paper
Title | Structural insights into Ubr1-mediated N-degron polyubiquitination. |
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Journal, issue, pages | Nature, Vol. 600, Issue 7888, Page 334-338, Year 2021 |
Publish date | Nov 17, 2021 |
Authors | 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 Abstract | 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. |
External links | Nature / PubMed:34789879 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.35 - 7.69 Å |
Structure data | EMDB-23806, PDB-7mex: EMDB-23807, PDB-7mey: EMDB-24935: EMDB-24936: |
Chemicals | ChemComp-ZN: ChemComp-Z3V: |
Source |
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Keywords | TRANSFERASE / Ubiquitin E3 ligase / ubiquitination / Ubr1 / Ubc2 / Degron / N-end rule |