RRC ID 53440
Author Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu JJ, Noda NN, Zhang H.
Title Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.
Journal Mol. Cell
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.
Volume 60(6)
Pages 914-29
Published 2015-12-17
DOI 10.1016/j.molcel.2015.11.019
PII S1097-2765(15)00911-9
PMID 26687600
MeSH Animals Autophagy* Autophagy-Related Protein 8 Family Binding Sites Caenorhabditis elegans / chemistry Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Crystallography, X-Ray Microtubule-Associated Proteins / chemistry* Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Models, Molecular Mutation Protein Conformation Protein-Serine-Threonine Kinases / metabolism Saccharomyces cerevisiae / chemistry Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / chemistry Saccharomyces cerevisiae Proteins / genetics
IF 14.548
Resource
C.elegans tm6474 tm2508 tm3425