Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition

  1. Zhu Liu
  2. Zhou Gong
  3. Wen-Xue Jiang
  4. Ju Yang
  5. Wen-Kai Zhu
  6. Da-Chuan Guo
  7. Wei-Ping Zhang
  8. Mai-Li Liu
  9. Chun Tang  Is a corresponding author
  1. Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, China
  2. Zhejiang University School of Medicine, China

Abstract

A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, a polyubiquitin is found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition.

Article and author information

Author details

  1. Zhu Liu

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Zhou Gong

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Wen-Xue Jiang

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Ju Yang

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Wen-Kai Zhu

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Da-Chuan Guo

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Wei-Ping Zhang

    Department of Pharmacology and Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Mai-Li Liu

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Chun Tang

    CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Wuhan, China
    For correspondence
    tanglab@wipm.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: November 25, 2014
  2. Accepted: June 18, 2015
  3. Accepted Manuscript published: June 19, 2015 (version 1)
  4. Version of Record published: July 20, 2015 (version 2)

Copyright

© 2015, Liu 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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  1. Zhu Liu
  2. Zhou Gong
  3. Wen-Xue Jiang
  4. Ju Yang
  5. Wen-Kai Zhu
  6. Da-Chuan Guo
  7. Wei-Ping Zhang
  8. Mai-Li Liu
  9. Chun Tang
(2015)
Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
eLife 4:e05767.
https://doi.org/10.7554/eLife.05767
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