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.

journal_name

Mol Cell

journal_title

Molecular cell

authors

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

doi

10.1016/j.molcel.2015.11.019

subject

Has Abstract

pub_date

2015-12-17 00:00:00

pages

914-29

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(15)00911-9

journal_volume

60

pub_type

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