
@article {69319,
	title = {Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Oct 22},
	abstract = {<p>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.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.49223},
	author = {Mohanty, Priyesh and Agrata, Rashmi and Habibullah, Batul Ismail and G S, Arun and Das, Ranabir}
}
