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

  1. Priyesh Mohanty
  2. Rashmi Agrata
  3. Batul Ismail Habibullah
  4. Arun Geetha Surendran
  5. Ranabir Das  Is a corresponding author
  1. National Center for Biological Sciences, Tata Institute of Fundamental Research, India
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Cite this article as: eLife 2019;8:e49223 doi: 10.7554/eLife.49223

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.

Article and author information

Author details

  1. Priyesh Mohanty

    National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Rashmi Agrata

    National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Batul Ismail Habibullah

    National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Arun Geetha Surendran

    National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Ranabir Das

    National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    For correspondence
    rana@ncbs.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5114-6817

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.

Reviewing Editor

  1. Lewis E Kay, University of Toronto, Canada

Publication history

  1. Received: June 11, 2019
  2. Accepted: October 21, 2019
  3. Accepted Manuscript published: October 22, 2019 (version 1)

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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