Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.
|Title||Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Mohanty P, Agrata R, Habibullah BIsmail, S AG, Das R|
|Date Published||2019 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.
|PubMed Central ID||PMC6874479|
|Grant List||Intramural 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 /