1. Structural Biology and Molecular Biophysics
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Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding

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Cite this article as: eLife 2020;9:e50294 doi: 10.7554/eLife.50294

Abstract

Mammalian mitochondrial inner membrane fusion is mediated by optic atrophy 1 (OPA1). Under physiological conditions, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (L-OPA1) and a soluble short isoform (S-OPA1). A combination of L-OPA1 and S-OPA1 is essential for efficient membrane fusion; however, the relevant mechanism is not well understood. In this study, we investigate the cryo-electron microscopic structures of S-OPA1–coated liposomes in nucleotide-free and GTPγS-bound states. S-OPA1 exhibits a general dynamin-like structure and can assemble onto membranes in a helical array with a dimer building block. We reveal that hydrophobic residues in its extended membrane-binding domain are critical for its tubulation activity. The binding of GTPγS triggers a conformational change and results in a rearrangement of the helical lattice and tube expansion similar to that of S-Mgm1. These observations indicate that S-OPA1 adopts a dynamin-like power stroke membrane remodeling mechanism during mitochondrial inner membrane fusion.

Data availability

Cryo-EM maps of S-OPA1 196-252 coated tubes have been deposited into Electron Microscopy Data Bank with the accession codes EMD-9901 for the helical reconstruction of nucleotide-free state, EMD-9903 for the tomographic reconstruction of nucleotide-free state and EMD-9902 for the tomographic reconstruction of GTPγS bound state, respectively. Sub-tomogram averaged cryo-EM map of wild type S-OPA1 coated tubes is also deposited with the accession code of EMD-0722. The raw data of GTPase assay in this study has been included as a supporting file.

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Article and author information

Author details

  1. Danyang Zhang

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Yan Zhang

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Jun Ma

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Chunmei Zhu

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Tongxin Niu

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Wenbo Chen

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaoyun Pang

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yujia Zhai

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Fei Sun

    Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    For correspondence
    feisun@ibp.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0351-5144

Funding

National Natural Science Foundation of China (31770794)

  • Yan Zhang

Chinese Academy of Sciences (XDB08030202)

  • Fei Sun

Ministry of Science and Technology of the People's Republic of China (2017YFA0504700)

  • Fei Sun

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

Reviewing Editor

  1. Hitoshi Nakatogawa, Tokyo Institute of Technology, Japan

Publication history

  1. Received: July 17, 2019
  2. Accepted: March 30, 2020
  3. Accepted Manuscript published: March 31, 2020 (version 1)
  4. Version of Record published: April 14, 2020 (version 2)

Copyright

© 2020, Zhang 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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