Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy

Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-15

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

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.

Peer Review Status:Awaiting Review

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