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.
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.
- Akinori Yamasaki
- Nobuo N Noda
- Nobuo N Noda
- Jian-Qiu Wu
- Li-Lin Du
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Noboru Mizushima, The University of Tokyo, Japan
© 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.