Journal
NATURE
Volume 600, Issue 7888, Pages 334-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-04097-8
Keywords
-
Categories
Funding
- Chicago Biomedical Consortium [C-086]
- National Institute of General Medical Sciences of the National Institutes of Health (NIH) [R35GM143052]
- National Key R&D Program of China [2017YFA0505200]
- NSFC [91753205, 81621002, 21621003]
- National Postdoctoral Program for Innovative Talents [BX2021143]
- Shuimu Tsinghua Scholar Program [2021SM067]
- National Cancer Institute's National Cryo-EM Facility at the Frederick National Laboratory for Cancer Research [HSSN261200800001E]
- National Science Foundation [2030381]
- University of Washington Bothell [74-0525]
- NIH [R01GM129325]
- Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases
- Direct For Biological Sciences
- Div Of Biological Infrastructure [2030381] Funding Source: National Science Foundation
Ask authors/readers for more resources
This study reveals the mechanism of the N-degron pathway mediated by Ubr1, including key structural elements involved in the initiation and elongation steps of ubiquitination.
The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation(1). In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N-degron pathway(2). 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available