Abstract
The Atg20 and Snx4/Atg24 proteins have been identified in a screen for mutants defective in a type of selective macroautophagy/autophagy. Both proteins are connected to the Atg1 kinase complex, which is involved in autophagy initiation, and bind phosphatidylinositol-3-phosphate. Atg20 and Snx4 contain putative BAR domains, suggesting a possible role in membrane deformation, but they have been relatively uncharacterized. Here we demonstrate that, in addition to its function in selective autophagy, Atg20 plays a critical role in the efficient induction of nonselective autophagy. Atg20 is a dynamic posttranslationally modified protein that engages both structurally stable (PX and BAR) and intrinsically disordered domains for its function. In addition to its PX and BAR domains, Atg20 uses a third membrane-binding module, a membrane-inducible amphipathic helix present in a previously undescribed location in Atg20 within the putative BAR domain. Taken together, these findings yield insights into the molecular mechanism of the autophagy machinery.
Keywords:
autophagy; vacuole; yeast.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Motifs
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Autophagy / genetics*
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Autophagy-Related Proteins / chemistry*
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Autophagy-Related Proteins / genetics
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Autophagy-Related Proteins / metabolism
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Binding Sites
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Cloning, Molecular
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Gene Expression Regulation, Fungal*
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Kinetics
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Models, Molecular
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Signal Transduction
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Sorting Nexins / chemistry*
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Sorting Nexins / genetics
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Sorting Nexins / metabolism
Substances
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Atg20 protein, S cerevisiae
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Autophagy-Related Proteins
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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Sorting Nexins