Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein
- National Institute of Biological Sciences, China
- Microbial Chemistry Research Foundation, Japan
- Ohio State University, United States
- Tokyo Institute of Technology, Japan
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.
Article and author information
Author details
Hitoshi Nakatogawa
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
- Noboru Mizushima, The University of Tokyo, Japan
Version history
- Received: August 19, 2018
- Accepted: November 18, 2018
- Accepted Manuscript published: November 19, 2018 (version 1)
- 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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Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein
eLife 7:e41237.
https://doi.org/10.7554/eLife.41237
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