title: The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes.
abstract: Autophagosome formation in yeast entails starvation-induced assembly of the pre-autophagosomal structure (PAS), in which multiple Atg1 complexes (composed of Atg1, Atg13, and the Atg17-Atg29-Atg31 subcomplex) are initially engaged. However, the molecular mechanisms underlying the multimeric assembly of these complexes remain unclear. Using structural and biological techniques, we herein demonstrate that Atg13 has a large intrinsically disordered region (IDR) and interacts with two distinct Atg17 molecules using two binding regions in the IDR. We further reveal that these two binding regions are essential not only for Atg1 complex assembly in vitro, but also for PAS organization in vivo. These findings underscore the structural and functional significance of the IDR of Atg13 in autophagy initiation: Atg13 provides intercomplex linkages between Atg17-Atg29-Atg31 complexes, thereby leading to supramolecular self-assembly of Atg1 complexes, in turn accelerating the initial events of autophagy, including autophosphorylation of Atg1, recruitment of Atg9 vesicles, and phosphorylation of Atg9 by Atg1.
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
authors.forename: Hayashi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujioka
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
authors.forename: Sho W
authors.initials: SW
authors.lastname: Suzuki
authors.affiliation: Department of Physics, College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Noshiro
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kondo-Kakuta
authors.affiliation: Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Department of Physics, College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ando
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan. Electronic address: nn@bikaken.or.jp.
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Noda
authors.affiliation: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan. Electronic address: yohsumi@iri.titech.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohsumi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C413216:ATG13 protein, S cerevisiae; C434065:ATG9 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; C505602:Atg17 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D064267:Intrinsically Disordered Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae