Mechanism-based small molecule cross-linkers of HECT E3 ubiquitin ligase-substrate pairs

Sungjin Park, Ioanna Ntai, Paul Thomas, Evgeniia Konishcheva, Neil L. Kelleher, Alexander V. Statsuk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Here we report the discovery that bifunctional thiol- and amine-reactive electrophiles serve as mechanism-based covalent cross-linkers for HECT E3 ubiquitin ligase-substrate pairs. We demonstrate that these chemical cross-linkers covalently cross-link the catalytic Cys residue of the yeast HECT E3 ubiquitin ligase Rsp5 with the Lys of the ubiquitination site in the model substrate Sic60-GFP. This work represents the first example of a mechanism-based covalent cross-link of HECT E3-substrate pairs that converts transiently interacting HECT E3-substrate pairs into stable, covalently cross-linked protein complexes, thereby facilitating their subsequent isolation, identification, and study.

Original languageEnglish (US)
Pages (from-to)8327-8329
Number of pages3
Issue number42
StatePublished - Oct 23 2012

ASJC Scopus subject areas

  • Biochemistry

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