title: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.
abstract: Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institute of Microbial Chemistry, Tokyo 141-0021, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Guo
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Microbial Chemistry, Tokyo 141-0021, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujioka
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Jin-Qi
authors.initials: JQ
authors.lastname: Ren
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
authors.forename: Tian-Cheng
authors.initials: TC
authors.lastname: Fang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, P.R. China.
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Shen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: Institute of Microbial Chemistry, Tokyo 141-0021, Japan. Electronic address: nn@bikaken.or.jp.
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Noda
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China. Electronic address: hongzhang@sun5.ibp.ac.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D029742:Caenorhabditis elegans Proteins; C587195:LGG-1 protein, C elegans; C587196:LGG-2 protein, C elegans; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases
keywords: Atg8; aggrephagy; autophagosome; lgg-1; lgg-2