title: Small differences make a big impact: Structural insights into the differential function of the 2 Atg8 homologs in C. elegans.
abstract: The 2 C. elegans homologs of Atg8, LGG-1 and LGG-2, show differential function in the degradation of protein aggregates during embryogenesis. LGG-1 is essential for the degradation of various protein aggregates, while LGG-2 has cargo-specific and developmental stage-specific roles. LGG-1 and LGG-2 differentially interact with autophagy substrates and ATG proteins. LGG-1 and LGG-2 possess 2 hydrophobic pockets, the W-site and the L-site, which recognize the LIR motif in Atg8-binding proteins. The plasticity of the W-site and the size and shape of the L-site differ between LGG-1 and LGG-2, thus determining their preferences for distinct LIR motifs. The N-terminal tails of LGG-1 and LGG-2 adopt unique closed and open conformations, respectively, which may result in distinct membrane tethering and fusion activities. LGG-1 and LGG-2 have different affinities for ATG-7 and ATG-3, and lipidation of LGG-2 is regulated by levels of lipidated LGG-1. Taken together, the structural differences between LGG-1 and LGG-2 provide insights into their differential functions in the aggrephagy pathway.
authors.affiliation: a National Laboratory of Biomacromolecules , Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: b School of Basic Medical Sciences , Anhui Medical University , Hefei , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: b School of Basic Medical Sciences , Anhui Medical University , Hefei , China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Shen
authors.affiliation: c Institute of Microbial Chemistry , Tokyo , Japan.
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Noda
authors.affiliation: a National Laboratory of Biomacromolecules , Institute of Biophysics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D008561:Membrane Fusion; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; C587195:LGG-1 protein, C elegans; C587196:LGG-2 protein, C elegans; D008869:Microtubule-Associated Proteins
keywords: Atg8; C. elegans; aggrephagy; lgg-1; lgg-2