Internal Ubiquitin Electrophiles for Covalent Trapping and Inhibition of Deubiquitinases.

ABSTRACT: The ubiquitin (Ub) system governs vital cellular processes in eukaryotic biology through an intricate network of Ub-protein interactions. While semisynthetic C-terminal Ub electrophiles (UbEs) are widely used to study Ub transfer and deubiquitinase (Dub) activity, they are limited to probing the active site while leaving other functionally important sites unexplored. Building on previously identified multivalent interaction interfaces and potential allosteric sites which are key to understanding their dynamic nature, here we report the development of genetically encoded Ub-based probes to covalently tether Ub-protein interactions in a proximity-driven manner at distal locations away from the active site. This study demonstrates that UbEs with internal electrophiles maintain conformational

SUBMITTER: Pannala NM 

PROVIDER: S-EPMC12631012 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature