Structure of Atg5.Atg16, a complex essential for autophagy. (original) (raw)
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| Title: | Structure of Atg5.Atg16, a complex essential for autophagy. |
|---|---|
| Authors: | Matsushita, Minako |
| Suzuki, Nobuo N. Browse this author | |
| Obara, Keisuke Browse this author | |
| Fujioka, Yuko Browse this author | |
| Ohsumi, Yoshinori Browse this author | |
| Inagaki, Fuyuhiko Browse this author | |
| Issue Date: | 2-Mar-2007 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 282 |
| Issue: | 9 |
| Start Page: | 6763 |
| End Page: | 6772 |
| Publisher DOI: | 10.1074/jbc.M609876200 |
| PMID: | 17192262 |
| Abstract: | Atg5 is covalently modified with a ubiquitin-like modifier, Atg12, and the Atg12-Atg5 conjugate further forms a complex with the multimeric protein Atg16. The Atg12-Atg5·Atg16 multimeric complex plays an essential role in autophagy, the bulk degradation system conserved in all eukaryotes. We have reported here the crystal structure of Atg5 complexed with the N-terminal region of Atg16 at 1.97Å resolution. Atg5 comprises two ubiquitin-like domains that flank a helix-rich domain. The N-terminal region of Atg16 has a helical structure and is bound to the groove formed by these three domains. In vitro analysis showed that Arg-35 and Phe-46 of Atg16 are crucial for the interaction. Atg16, with a mutation at these residues, failed to localize to the pre-autophagosomal structure and could not restore autophagy in Atg16-deficient yeast strains. Furthermore, these Atg16 mutants could not restore a severe reduction in the formation of the Atg8-phosphatidylethanolamine conjugate, another essential factor for autophagy, in Atg16-deficient strains under starvation conditions. These results taken together suggest that the direct interaction between Atg5 and Atg16 is crucial to the performance of their roles in autophagy. |
| Rights: | Copyright © 2007 by the American Society for Biochemistry and Molecular Biology |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/22079 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc) |
Submitter: 稲垣 冬彦