1. Cell Biology
  2. Structural Biology and Molecular Biophysics
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Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein

  1. Xiao-Man Liu
  2. Akinori Yamasaki
  3. Xiao-Min Du
  4. Valerie C Coffman
  5. Yoshinori Ohsumi
  6. Hitoshi Nakatogawa
  7. Jian-Qiu Wu
  8. Nobuo N Noda  Is a corresponding author
  9. Li-Lin Du  Is a corresponding author
  1. National Institute of Biological Sciences, China
  2. Microbial Chemistry Research Foundation, Japan
  3. Ohio State University, United States
  4. Tokyo Institute of Technology, Japan
Research Article
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Cite this article as: eLife 2018;7:e41237 doi: 10.7554/eLife.41237

Abstract

The ubiquitin-like protein Atg8, in its lipidated form, plays central roles in autophagy. Yet, remarkably, Atg8 also carries out lipidation-independent functions in non-autophagic processes. How Atg8 performs its moonlighting roles is unclear. Here we report that in the fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae, the lipidation-independent roles of Atg8 in maintaining normal morphology and functions of the vacuole require its interaction with a vacuole membrane protein Hfl1 (homolog of human TMEM184 proteins). Crystal structures revealed that the Atg8-Hfl1 interaction is not mediated by the typical Atg8-family-interacting motif (AIM) that forms an intermolecular β-sheet with Atg8. Instead, the Atg8-binding regions in Hfl1 proteins adopt a helical conformation, thus representing a new type of AIMs (termed helical AIMs here). These results deepen our understanding of both the functional versatility of Atg8 and the mechanistic diversity of Atg8 binding.

Data availability

The atomic coordinates and reflection data of the crystal structures of fission yeast and budding yeast Atg8-Hfl1 complexes have been deposited in the Protein Data Bank under accession codes 6AAF and 6AAG, respectively.

The following data sets were generated

Article and author information

Author details

  1. Xiao-Man Liu

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  2. Akinori Yamasaki

    Institute of Microbial Chemistry, Microbial Chemistry Research Foundation, Tokyo, Japan
    Competing interests
    No competing interests declared.
  3. Xiao-Min Du

    National Institute of Biological Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  4. Valerie C Coffman

    Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
  5. Yoshinori Ohsumi

    Unit for Cell Biology, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan
    Competing interests
    No competing interests declared.
  6. Hitoshi Nakatogawa

    School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan
    Competing interests
    Hitoshi Nakatogawa, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5828-0741
  7. Jian-Qiu Wu

    Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
  8. Nobuo N Noda

    Institute of Microbial Chemistry, Microbial Chemistry Research Foundation, Tokyo, Japan
    For correspondence
    nn@bikaken.or.jp
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6940-8069
  9. Li-Lin Du

    National Institute of Biological Sciences, Beijing, China
    For correspondence
    dulilin@nibs.ac.cn
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1028-7397

Funding

Japan Society for the Promotion of Science

  • Akinori Yamasaki
  • Nobuo N Noda

Japan Science and Technology Agency

  • Nobuo N Noda

National Institute of General Medical Sciences

  • Jian-Qiu Wu

Ministry of Science and Technology of the People's Republic of China

  • Li-Lin Du

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

Reviewing Editor

  1. Noboru Mizushima, The University of Tokyo, Japan

Publication history

  1. Received: August 19, 2018
  2. Accepted: November 18, 2018
  3. Accepted Manuscript published: November 19, 2018 (version 1)
  4. Version of Record published: December 4, 2018 (version 2)

Copyright

© 2018, 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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