1. Structural Biology and Molecular Biophysics
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Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism

  1. Jingjing Guo
  2. Huan-Xiang Zhou  Is a corresponding author
  1. Henan Normal University, China
  2. Florida State University, United States
Research Article
  • Cited 3
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Cite this article as: eLife 2016;5:e18249 doi: 10.7554/eLife.18249

Abstract

Small ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The β-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that binding of the β-grasp domain induces significant conformational and dynamic changes in SENP1, including widening of the exosite cleft and quenching of nanosecond dynamics in all but a distal region. A dock-and-coalesce mechanism emerges for SENP-catalyzed SUMO cleavage: the wedging of the β-grasp domain enables the docking of the proximal portion of the C-terminus and the strengthened cross-channel motional coupling initiates inter-subdomain correlated motions to allow for the distal portion to coalesce around the catalytic center.

Article and author information

Author details

  1. Jingjing Guo

    Henan Engineering Research Center of Chiral Hydroxyl Pharmaceuticals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Huan-Xiang Zhou

    Department of Physics, Institute of Molecular Biophysics, Florida State University, Tallahassee, United States
    For correspondence
    hzhou4@fsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9020-0302

Funding

National Institutes of Health (GM058187)

  • Huan-Xiang Zhou

National Institutes of Health (GM118091)

  • Huan-Xiang Zhou

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: May 27, 2016
  2. Accepted: August 29, 2016
  3. Accepted Manuscript published: August 31, 2016 (version 1)
  4. Version of Record published: September 20, 2016 (version 2)

Copyright

© 2016, Guo & Zhou

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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