title: Structural basis of starvation-induced assembly of the autophagy initiation complex.
abstract: 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.
authors.affiliation: 1] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2].
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujioka
authors.affiliation: 1] Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan. [2] Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. [3].
authors.forename: Sho W
authors.initials: SW
authors.lastname: Suzuki
authors.affiliation: 1] Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan. [2].
authors.forename: Hayashi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kondo-Kakuta
authors.affiliation: Graduate School of Medical Life Science and Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Graduate School of Medical Life Science and Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Rinji
authors.initials: R
authors.lastname: Akada
authors.affiliation: 1] Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan. [2] Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
authors.affiliation: 1] Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. [2] Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Noda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D012694:Serine / Q000737:chemistry / Q000378:metabolism
chemical_list: C413216:ATG13 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; C505602:Atg17 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae