Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases.
Elife
; 82019 10 22.
Article
in En
| MEDLINE
| ID: mdl-31638574
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 (TRAF6RING) 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/TRAF6RING 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Shigella flexneri
/
Bacterial Proteins
/
Protein Processing, Post-Translational
/
Ubiquitin-Conjugating Enzymes
/
Intracellular Signaling Peptides and Proteins
/
Amidohydrolases
Language:
En
Journal:
Elife
Year:
2019
Document type:
Article
Affiliation country:
India