Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B‐positive structures |
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| Authors: | Alf Håkon Lystad Yoshinobu Ichimura Kenji Takagi Yinjie Yang Serhiy Pankiv Yumi Kanegae Shun Kageyama Mariko Suzuki Izumu Saito Tsunehiro Mizushima Masaaki Komatsu Anne Simonsen |
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| Institution: | 1. Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;2. Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;3. Picobiology Institute, Graduate School of Life Science, University of Hyogo, Hyogo, Japan;4. Laboratory of Molecular Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan |
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| 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. |
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| Keywords: |
ALFY
GABARAP
LC3
LIR
structure |
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