摘要: 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.
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期刊:
MOLECULAR CELL
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分类:
生物学
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生物物理学
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生物物理、生物化学与分子生物学
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引用:
ChinaXiv:201605.01733
(或此版本
ChinaXiv:201605.01733V1)
doi:10.12074/201605.01733
CSTR:32003.36.ChinaXiv.201605.01733.V1
- 推荐引用方式:
Wu, Fan,Qi, Xin,Zhao, Hong-Yu,Wang, Zheng,Zhang, Hui,Ren, Jin-Qi,Feng, Wei,Hu, Jun-Jie,Zhang, Hong,Watanabe, Yasunori,Fujioka, Yuko,Noda, Nobuo N.,Guo, Xiang-Yang,Fang, Tian-Cheng,Wang, Peng,Shen, Yu-Xian.(2016).Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.MOLECULAR CELL.[ChinaXiv:201605.01733]
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