Structural insights into Ubr1-mediated N-degron polyubiquitination.

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 re

SUBMITTER: Pan M 

PROVIDER: S-EPMC8798225 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature