Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.

ABSTRACT: The deamidase OspI from enteric bacteria Shigella flexneri 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^RING) 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^RING interface. Moreover, the salt-bridge competitio

SUBMITTER: Mohanty P 

PROVIDER: S-EPMC6874479 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature