Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8

Seung Beom Hong; Byeong Won Kim; Kyung Eun Lee; Se Woong Kim; Hyesung Jeon; Joon Kim; Hyun Kyu Song

doi:10.1038/nsmb.2165

Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8

Seung Beom Hong, Byeong Won Kim, Kyung Eun Lee, Se Woong Kim, Hyesung Jeon, Joon Kim, Hyun Kyu Song

Research output: Contribution to journal › Article › peer-review

83 Citations (Scopus)

Abstract

Autophagy is the degradation of cellular organelles via the lysosomal pathway. The autophagic ubiquitin-like (Ubl) molecule Atg8 is activated by the E1-like enzyme Atg7. As this noncanonical E1 enzyme's domain organization is unique among Ubl-activating E1 enzymes, the structural basis for its interactions with Atg8 and partner E2 enzymes remains obscure. Here we present the structure of the N-terminal domain of Atg7, revealing a unique protein fold and interactions with both autophagic E2 enzymes Atg3 and Atg10. The structure of the C-terminal domain of Atg7 in complex with Atg8 shows the mode of dimerization and mechanism of recognition of Atg8. Notably, the catalytic cysteine residue in Atg7 is positioned close to the C-terminal glycine of Atg8, its target for thioester formation, potentially eliminating the need for large conformational rearrangements characteristic of other E1s.

Original language	English
Pages (from-to)	1323-1330
Number of pages	8
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	12
DOIs	https://doi.org/10.1038/nsmb.2165
Publication status	Published - 2011 Dec

Bibliographical note

Funding Information:
We thank the staff at 4A beamline, Pohang Accelerator Laboratory, South Korea, and NE3A and NW12 beamline, Photon Factory, Japan, for help with the data collection; H. Nakatogawa and Y. Ohsumi (Tokyo Institute of Technology), W.K. Huh (Seoul National University), C.W. Yun (Korea University), D.J. Klionsky (University of Michigan) for yeast strains; and M.J. Eck for critical comments on the manuscript. This work was supported by the WorldClass University Project (R3310108), the 21C Frontier Functional Proteomics Project (FPR08B2270) and the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092006 and A084016).

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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title = "Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8",

abstract = "Autophagy is the degradation of cellular organelles via the lysosomal pathway. The autophagic ubiquitin-like (Ubl) molecule Atg8 is activated by the E1-like enzyme Atg7. As this noncanonical E1 enzyme's domain organization is unique among Ubl-activating E1 enzymes, the structural basis for its interactions with Atg8 and partner E2 enzymes remains obscure. Here we present the structure of the N-terminal domain of Atg7, revealing a unique protein fold and interactions with both autophagic E2 enzymes Atg3 and Atg10. The structure of the C-terminal domain of Atg7 in complex with Atg8 shows the mode of dimerization and mechanism of recognition of Atg8. Notably, the catalytic cysteine residue in Atg7 is positioned close to the C-terminal glycine of Atg8, its target for thioester formation, potentially eliminating the need for large conformational rearrangements characteristic of other E1s.",

author = "Hong, {Seung Beom} and Kim, {Byeong Won} and Lee, {Kyung Eun} and Kim, {Se Woong} and Hyesung Jeon and Joon Kim and Song, {Hyun Kyu}",

note = "Funding Information: We thank the staff at 4A beamline, Pohang Accelerator Laboratory, South Korea, and NE3A and NW12 beamline, Photon Factory, Japan, for help with the data collection; H. Nakatogawa and Y. Ohsumi (Tokyo Institute of Technology), W.K. Huh (Seoul National University), C.W. Yun (Korea University), D.J. Klionsky (University of Michigan) for yeast strains; and M.J. Eck for critical comments on the manuscript. This work was supported by the WorldClass University Project (R3310108), the 21C Frontier Functional Proteomics Project (FPR08B2270) and the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092006 and A084016).",

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AU - Jeon, Hyesung

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Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8

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