Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases
- National Center for Biological Sciences, Tata Institute of Fundamental Research, India
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-kB 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 where a post-translational modification perturbs the conformation and stability of transient complexes to inhibit protein-protein association.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
Tata Institute of Fundamental Research (Intramural grant)
- Ranabir Das
Department of Biotechnology , Ministry of Science and Technology (Ramalingaswamy Fellowship)
- Ranabir Das
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Mohanty et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases
eLife 8:e49223.
https://doi.org/10.7554/eLife.49223
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