title: Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures.
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.
authors.affiliation: Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Alf Håkon
authors.initials: AH
authors.lastname: Lystad
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ichimura
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Yang
authors.forename: Serhiy
authors.initials: S
authors.lastname: Pankiv
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kanegae
authors.forename: Shun
authors.initials: S
authors.lastname: Kageyama
authors.forename: Mariko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Izumu
authors.initials: I
authors.lastname: Saito
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mizushima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Anne
authors.initials: A
authors.lastname: Simonsen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; C116741:GABARAP protein, human; C498698:GABARAPL2 protein, human; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C499825:WDFY3 protein, human