Structural basis of starvation-induced assembly of the autophagy initiation complex

被引：194

作者：

Fujioka, Yuko ^{[1
]}

Suzuki, Sho W. ^{[2
,3
]}

Yamamoto, Hayashi ^{[2
]}

Kondo-Kakuta, Chika ^{[2
]}

Kimura, Yayoi ^{[4
,5
]}

Hirano, Hisashi ^{[4
,5
]}

Akada, Rinji ^{[6
]}

Inagaki, Fuyuhiko ^{[7
,8
]}

Ohsumi, Yoshinori ^{[2
]}

Noda, Nobuo N. ^{[1
,8
]}

机构：

[1] Inst Microbial Chem BIKAKEN, Tokyo, Japan

[2] Tokyo Inst Technol, Frontier Res Ctr, Yokohama, Kanagawa 227, Japan

[3] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 227, Japan

[4] Yokohama City Univ, Grad Sch Med Life Sci, Yokohama, Kanagawa 232, Japan

[5] Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 232, Japan

[6] Yamaguchi Univ, Grad Sch Med, Dept Appl Mol Biosci, Ube, Yamaguchi 755, Japan

[7] Hokkaido Univ, Dept Biol Struct, Fac Adv Life Sci, Sapporo, Hokkaido, Japan

[8] Japan Sci & Technol Agcy, Core Res Evolutionary Sci & Technol, Tokyo, Japan

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2014年 / 21卷 / 06期

关键词：

PROTEIN-KINASE COMPLEX; SACCHAROMYCES-CEREVISIAE; TOR; ATG1; YEAST; RECRUITMENT; INDUCTION; SCAFFOLD;

D O I：

10.1038/nsmb.2822

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Assembly of the preautophagosomal structure (PAS) is essential for autophagy initiation in yeast. Starvation-induced dephosphorylation of Atg13 is required for the formation of the Atg1-Atg13-Atg17-Atg29-Atg31 complex (Atg1 complex), a prerequisite for PAS assembly. However, molecular details underlying these events have not been established. Here we studied the interactions of yeast Atg13 with Atg1 and Atg17 by X-ray crystallography. Atg13 binds tandem microtubule interacting and transport domains in Atg1, using an elongated helix-loop-helix region. Atg13 also binds Atg17, using a short region, thereby bridging Atg1 and Atg17 and leading to Atg1-complex formation. Dephosphorylation of specific serines in Atg13 enhanced its interaction with not only Atg1 but also Atg17. These observations update the autophagy-initiation model as follows: upon starvation, dephosphorylated Atg13 binds both Atg1 and Atg17, and this promotes PAS assembly and autophagy progression.

引用

页码：513 / 521

页数：9

共 28 条

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