The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes

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...

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Vydané v:Developmental cell Ročník 38; číslo 1; s. 86 - 99
Hlavní autori: Yamamoto, Hayashi, Fujioka, Yuko, Suzuki, Sho W, Noshiro, Daisuke, Suzuki, Hironori, Kondo-Kakuta, Chika, Kimura, Yayoi, Hirano, Hisashi, Ando, Toshio, Noda, Nobuo N, Ohsumi, Yoshinori
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 11.07.2016
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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.
AbstractList 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.
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.
Author Ohsumi, Yoshinori
Ando, Toshio
Fujioka, Yuko
Noshiro, Daisuke
Noda, Nobuo N
Suzuki, Hironori
Hirano, Hisashi
Suzuki, Sho W
Yamamoto, Hayashi
Kondo-Kakuta, Chika
Kimura, Yayoi
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  surname: Yamamoto
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  organization: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan
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  surname: Fujioka
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  organization: Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan
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  givenname: Sho W
  surname: Suzuki
  fullname: Suzuki, Sho W
  organization: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan
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  givenname: Daisuke
  surname: Noshiro
  fullname: Noshiro, Daisuke
  organization: Department of Physics, College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan
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  givenname: Hironori
  surname: Suzuki
  fullname: Suzuki, Hironori
  organization: Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan
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  surname: Hirano
  fullname: Hirano, Hisashi
  organization: Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
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  surname: Ando
  fullname: Ando, Toshio
  organization: Department of Physics, College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan
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  givenname: Nobuo N
  surname: Noda
  fullname: Noda, Nobuo N
  email: nn@bikaken.or.jp
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  givenname: Yoshinori
  surname: Ohsumi
  fullname: Ohsumi, Yoshinori
  email: yohsumi@iri.titech.ac.jp
  organization: Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan. Electronic address: yohsumi@iri.titech.ac.jp
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Snippet Autophagosome formation in yeast entails starvation-induced assembly of the pre-autophagosomal structure (PAS), in which multiple Atg1 complexes (composed of...
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SubjectTerms Adaptor Proteins, Signal Transducing - chemistry
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Amino Acid Sequence
Autophagy
Autophagy-Related Proteins - chemistry
Autophagy-Related Proteins - genetics
Autophagy-Related Proteins - metabolism
Intrinsically Disordered Proteins - chemistry
Intrinsically Disordered Proteins - genetics
Intrinsically Disordered Proteins - metabolism
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Multiprotein Complexes - chemistry
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Phagosomes - physiology
Phosphorylation
Protein Binding
Protein Conformation
Protein Kinases - chemistry
Protein Kinases - genetics
Protein Kinases - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - growth & development
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Sequence Homology, Amino Acid
Title The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes
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