Abstract
Several autophagy proteins contain an LC3-interacting region (LIR) responsible for their interaction with Atg8 homolog proteins. Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy. In addition, the crystal structure of the GABARAP-ALFY-LIR peptide complex identifies three conserved residues in the GABARAPs that are responsible for binding to ALFY. Interestingly, introduction of these residues in LC3B is sufficient to enable its interaction with ALFY, indicating that residues outside the LIR-binding hydrophobic pockets confer specificity to the interactions with Atg8 homolog proteins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Apoptosis Regulatory Proteins
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Autophagy*
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Autophagy-Related Protein 8 Family
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Autophagy-Related Proteins
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Cell Line, Tumor
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HeLa Cells
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Humans
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Hydrophobic and Hydrophilic Interactions
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Membrane Proteins / metabolism*
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Membrane Proteins / ultrastructure
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Microfilament Proteins / metabolism
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Microtubule-Associated Proteins / genetics*
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Microtubule-Associated Proteins / metabolism*
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Microtubule-Associated Proteins / ultrastructure
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Protein Binding
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Protein Structure, Tertiary
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Alignment
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Transcription Factors / metabolism*
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Transcription Factors / ultrastructure
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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Autophagy-Related Protein 8 Family
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Autophagy-Related Proteins
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GABARAP protein, human
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GABARAPL2 protein, human
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MAP1LC3B protein, human
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Membrane Proteins
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Microfilament Proteins
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Microtubule-Associated Proteins
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Recombinant Proteins
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Transcription Factors
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WDFY3 protein, human