1. Structural Biology and Molecular Biophysics
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Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions

  1. Keyu Chen
  2. Jianchao Li
  3. Chao Wang
  4. Zhiyi Wei
  5. Mingjie Zhang  Is a corresponding author
  1. The Hong Kong University of Science and Technology, Hong Kong
  2. Hong Kong University of Science and Technology, China
  3. University of Science and Technology of China, China
  4. South University of Science and Technology of China, China
Research Article
  • Cited 12
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Cite this article as: eLife 2017;6:e29150 doi: 10.7554/eLife.29150

Abstract

Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility of the target binding groove of ANK repeats must be regulated to achieve spatially defined functions of ankyrins/target complexes in different tissues, though little is known in this regard. Here we systemically investigated the autoinhibition mechanism of ankyrin-B/G by combined biochemical, biophysical and structural biology approaches. We discovered that the entire ANK repeats are inhibited by combinatorial and quasi-independent bindings of multiple disordered segments located in the ankyrin-B/G linkers and tails, suggesting a mechanistic basis for differential regulations of membrane target bindings by ankyrins. In addition to elucidating the autoinhibition mechanisms of ankyrins, our study may also shed light on regulations on target bindings by other long repeat-containing proteins.

Article and author information

Author details

  1. Keyu Chen

    Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, Hong Kong
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0321-0604
  2. Jianchao Li

    Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China
    Competing interests
    No competing interests declared.
  3. Chao Wang

    School of Life Sciences, University of Science and Technology of China, Hefei, China
    Competing interests
    No competing interests declared.
  4. Zhiyi Wei

    Department of Biology, South University of Science and Technology of China, Shenzhen, China
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4446-6502
  5. Mingjie Zhang

    Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, Hong Kong
    For correspondence
    mzhang@ust.hk
    Competing interests
    Mingjie Zhang, Reviewing editor, eLife..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9404-0190

Funding

Research Grants Council, University Grants Committee (663812)

  • Mingjie Zhang

Ministry of Science and Technology of the People's Republic of China (2014CB910204)

  • Mingjie Zhang

Research Grants Council, University Grants Committee (664113)

  • Mingjie Zhang

Research Grants Council, University Grants Committee (16103614)

  • Mingjie Zhang

Research Grants Council, University Grants Committee (AoE-M09-12)

  • Mingjie Zhang

Ministry of Science and Technology of the People's Republic of China (2016YFA0501900)

  • Mingjie Zhang

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

Reviewing Editor

  1. Axel T Brunger, Stanford University Medical Center, United States

Publication history

  1. Received: May 31, 2017
  2. Accepted: August 24, 2017
  3. Accepted Manuscript published: August 25, 2017 (version 1)
  4. Version of Record published: September 20, 2017 (version 2)

Copyright

© 2017, Chen 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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