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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Published in:Developmental cell Vol. 38; no. 1; pp. 86 - 99
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 11.07.2016
Subjects:
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
ISSN:1878-1551
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Summary: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.
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ISSN:1878-1551
DOI:10.1016/j.devcel.2016.06.015