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A semisynthetic Atg3 reveals that acetylation promotes Atg3 membrane binding and Atg8 lipidation.

ABSTRACT: Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to phosphatidylethanolamine-containing liposomes and to endoplasmic reticulum, through which it promotes the lipidation process.

SUBMITTER: Li YT

PROVIDER: S-EPMC5473643 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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A semisynthetic Atg3 reveals that acetylation promotes Atg3 membrane binding and Atg8 lipidation.

Li Yi-Tong YT Yi Cong C Chen Chen-Chen CC Lan Huan H Pan Man M Zhang Shao-Jin SJ Huang Yi-Chao YC Guan Chao-Jian CJ Li Yi-Ming YM Yu Li L Liu Lei L

Nature communications 20170322

Acetylation of Atg3 regulates the lipidation of the protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe the first semi-synthesis of homogeneous K19/K48-diacetylated Atg3 through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with the semi-synthetic proteins confirm that Atg3 acetylation can promote the lipidation of Atg8. We find that acetylation of Atg3 enhances its binding to ...[more]

PMID: 28327644

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