7JLO

Cryo-EM structure of human ATG9A in amphipols

7JLO の概要

• エントリーDOI: 10.2210/pdb7jlo/pdb
• EMDBエントリー: 22375 22376 22377
• 分子名称: Autophagy-related protein 9A (1 entity in total)
• 機能のキーワード: autophagy, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 200392.03

構造登録者

Maeda, S.,Otomo, T. (登録日: 2020-07-30, 公開日: 2020-10-28, 最終更新日: 2024-10-23)

主引用文献

Maeda, S.,Yamamoto, H.,Kinch, L.N.,Garza, C.M.,Takahashi, S.,Otomo, C.,Grishin, N.V.,Forli, S.,Mizushima, N.,Otomo, T.
Structure, lipid scrambling activity and role in autophagosome formation of ATG9A.
Nat.Struct.Mol.Biol., 27:1194-1201, 2020

PubMed Abstract: De novo formation of the double-membrane compartment autophagosome is seeded by small vesicles carrying membrane protein autophagy-related 9 (ATG9), the function of which remains unknown. Here we find that ATG9A scrambles phospholipids of membranes in vitro. Cryo-EM structures of human ATG9A reveal a trimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Similarities to ABC exporters suggest that ATG9A could be a transporter that uses the central pore to function. Moreover, molecular dynamics simulation suggests that the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipids to flip. Mutations in the pore reduce scrambling activity and yield markedly smaller autophagosomes, indicating that lipid scrambling by ATG9A is essential for membrane expansion. We propose ATG9A acts as a membrane-embedded funnel to facilitate lipid flipping and to redistribute lipids added to the outer leaflet of ATG9 vesicles, thereby enabling growth into autophagosomes.

PubMed: 33106659
DOI: 10.1038/s41594-020-00520-2

実験手法

ELECTRON MICROSCOPY (3.4 Å)