Photoreactive crosslinkers capture the ubiquitin–E2–E3 ligases intermediates

Abstract

E3 ligases catalyze the final step in transferring ubiquitin to protein substrates, but resulting intermediates are characterized by conformational flexibility. Recent work by Chandler and colleagues ( Biochem J. (2026) 483, 1115–1130) demonstrates that photocross-linking activity-based probes can trap transient conformations of the intermediates, providing a valuable tool to map interfaces during the ubiquitin transfer process.