TitleDeamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.
Publication TypeJournal Article
Year of Publication2019
AuthorsMohanty P, Agrata R, Habibullah BIsmail, S AG, Das R
Date Published2019 Oct 22

The deamidase OspI from enteric bacteria deamidates a glutamine residue in the host ubiquitin-conjugating enzyme UBC13 and converts it to glutamate (Q100E). Consequently, its polyubiquitination activity in complex with the RING-finger ubiquitin ligase TRAF6 and the downstream NF-κB inflammatory response is silenced. The precise role of deamidation in silencing the UBC13/TRAF6 complex is unknown. We report that deamidation inhibits the interaction between UBC13 and TRAF6 RING-domain (TRAF6) by perturbing both the native and transient interactions. Deamidation creates a new intramolecular salt-bridge in UBC13 that competes with a critical intermolecular salt-bridge at the native UBC13/TRAF6 interface. Moreover, the salt-bridge competition prevents transient interactions necessary to form a typical UBC13/RING complex. Repulsion between E100 and the negatively charged surface of RING also prevents transient interactions in the UBC13/RING complex. Our findings highlight a mechanism wherein a post-translational modification perturbs the conformation and stability of transient complexes to inhibit protein-protein association.

Alternate JournalElife
PubMed ID31638574
PubMed Central IDPMC6874479
Grant ListIntramural grant / / Tata Institute of Fundamental Research /
Ramalingaswamy Fellowship / / Department of Biotechnology, Ministry of Science and Technology /
Ramalingaswamy Fellowship / / Department of Biotechnology , Ministry of Science and Technology /