Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein
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 Schizosaccharom...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/41237 |
| _version_ | 1811227874280079360 |
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| author | Xiao-Man Liu Akinori Yamasaki Xiao-Min Du Valerie C Coffman Yoshinori Ohsumi Hitoshi Nakatogawa Jian-Qiu Wu Nobuo N Noda Li-Lin Du |
| author_facet | Xiao-Man Liu Akinori Yamasaki Xiao-Min Du Valerie C Coffman Yoshinori Ohsumi Hitoshi Nakatogawa Jian-Qiu Wu Nobuo N Noda Li-Lin Du |
| author_sort | Xiao-Man Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:48:03Z |
| format | Article |
| id | doaj.art-cd1face10e8f4a43b93cd643d44bb34c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:48:03Z |
| publishDate | 2018-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-cd1face10e8f4a43b93cd643d44bb34c2022-12-22T03:37:53ZengeLife Sciences Publications LtdeLife2050-084X2018-11-01710.7554/eLife.41237Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane proteinXiao-Man Liu0Akinori Yamasaki1Xiao-Min Du2Valerie C Coffman3Yoshinori Ohsumi4Hitoshi Nakatogawa5https://orcid.org/0000-0002-5828-0741Jian-Qiu Wu6Nobuo N Noda7https://orcid.org/0000-0002-6940-8069Li-Lin Du8https://orcid.org/0000-0002-1028-7397National Institute of Biological Sciences, Beijing, ChinaInstitute of Microbial Chemistry, Tokyo, JapanNational Institute of Biological Sciences, Beijing, China; College of Life Sciences, Beijing Normal University, Beijing, ChinaThe Ohio State University, Columbus, United StatesUnit for Cell Biology, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, JapanSchool of Life Science and Technology, Tokyo Institute of Technology, Yokohama, JapanThe Ohio State University, Columbus, United StatesInstitute of Microbial Chemistry, Tokyo, JapanNational Institute of Biological Sciences, Beijing, ChinaThe 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.https://elifesciences.org/articles/41237autophagyvacuoleAtg8 |
| spellingShingle | Xiao-Man Liu Akinori Yamasaki Xiao-Min Du Valerie C Coffman Yoshinori Ohsumi Hitoshi Nakatogawa Jian-Qiu Wu Nobuo N Noda Li-Lin Du Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein eLife autophagy vacuole Atg8 |
| title | Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein |
| title_full | Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein |
| title_fullStr | Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein |
| title_full_unstemmed | Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein |
| title_short | Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein |
| title_sort | lipidation independent vacuolar functions of atg8 rely on its noncanonical interaction with a vacuole membrane protein |
| topic | autophagy vacuole Atg8 |
| url | https://elifesciences.org/articles/41237 |
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