8KC3

Cryo-EM structure of human C-terminally bound ATG9A-ATG2A-WIPI4 complex

8KC3 の概要

• エントリーDOI: 10.2210/pdb8kc3/pdb
• EMDBエントリー: 37091
• 分子名称: Autophagy-related protein 9A, WD repeat domain phosphoinositide-interacting protein 4, Autophagy-related protein 2 homolog A (3 entities in total)
• 機能のキーワード: lipid transfer, atg9a-atg2a-wipi4 complex, single particle cryo-em, autophagy, lipid transport-membrane protein complex, lipid transport/membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 536669.91

構造登録者

Wang, Y.,Stjepanovic, G. (登録日: 2023-08-05, 公開日: 2024-08-07, 最終更新日: 2025-01-29)

主引用文献

Wang, Y.,Dahmane, S.,Ti, R.,Mai, X.,Zhu, L.,Carlson, L.A.,Stjepanovic, G.
Structural basis for lipid transfer by the ATG2A-ATG9A complex.
Nat.Struct.Mol.Biol., 32:35-47, 2025

PubMed Abstract: Autophagy is characterized by the formation of double-membrane vesicles called autophagosomes. Autophagy-related proteins (ATGs) 2A and 9A have an essential role in autophagy by mediating lipid transfer and re-equilibration between membranes for autophagosome formation. Here we report the cryo-electron microscopy structures of human ATG2A in complex with WD-repeat protein interacting with phosphoinositides 4 (WIPI4) at 3.2 Å and the ATG2A-WIPI4-ATG9A complex at 7 Å global resolution. On the basis of molecular dynamics simulations, we propose a mechanism of lipid extraction from the donor membranes. Our analysis revealed 3:1 stoichiometry of the ATG9A-ATG2A complex, directly aligning the ATG9A lateral pore with ATG2A lipid transfer cavity, and an interaction of the ATG9A trimer with both the N-terminal and the C-terminal tip of rod-shaped ATG2A. Cryo-electron tomography of ATG2A liposome-binding states showed that ATG2A tethers lipid vesicles at different orientations. In summary, this study provides a molecular basis for the growth of the phagophore membrane and lends structural insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.

PubMed: 39174844
DOI: 10.1038/s41594-024-01376-6

実験手法

ELECTRON MICROSCOPY (7 Å)