An N-terminal conserved region in human Atg3 couples membrane curvature sensitivity to conjugase activity during autophagy Journal Article


Authors: Ye, Y.; Tyndall, E. R.; Bui, V.; Tang, Z.; Shen, Y.; Jiang, X.; Flanagan, J. M.; Wang, H. G.; Tian, F.
Article Title: An N-terminal conserved region in human Atg3 couples membrane curvature sensitivity to conjugase activity during autophagy
Abstract: During autophagy the enzyme Atg3 catalyzes the covalent conjugation of LC3 to the amino group of phosphatidylethanolamine (PE) lipids, which is one of the key steps in autophagosome formation. Here, we have demonstrated that an N-terminal conserved region of human Atg3 (hAtg3) communicates information from the N-terminal membrane curvature-sensitive amphipathic helix (AH), which presumably targets the enzyme to the tip of phagophore, to the C-terminally located catalytic core for LC3–PE conjugation. Mutations in the putative communication region greatly reduce or abolish the ability of hAtg3 to catalyze this conjugation in vitro and in vivo, and alter the membrane-bound conformation of the wild-type protein, as reported by NMR. Collectively, our results demonstrate that the N-terminal conserved region of hAtg3 works in concert with its geometry-selective AH to promote LC3–PE conjugation only on the target membrane, and substantiate the concept that highly curved membranes drive spatial regulation of the autophagosome biogenesis during autophagy. © 2021, The Author(s).
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-01-14
Start Page: 374
Language: English
DOI: 10.1038/s41467-020-20607-0
PROVIDER: scopus
PMCID: PMC7809043
PUBMED: 33446636
DOI/URL:
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
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  1. Xuejun Jiang
    121 Jiang