8DO8

Crystal structure ATG9 HDIR in complex with the ATG13:ATG101 HORMA dimer

8DO8 の概要

• エントリーDOI: 10.2210/pdb8do8/pdb
• 分子名称: Autophagy-related protein 101, Autophagy-related protein 13, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: horma, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 147397.58

構造登録者

Buffalo, C.Z.,Ren, X.,Yokom, A.L.,Hurley, J.H. (登録日: 2022-07-12, 公開日: 2022-11-23, 最終更新日: 2023-10-25)

主引用文献

Ren, X.,Nguyen, T.N.,Lam, W.K.,Buffalo, C.Z.,Lazarou, M.,Yokom, A.L.,Hurley, J.H.
Structural basis for ATG9A recruitment to the ULK1 complex in mitophagy initiation.
Sci Adv, 9:eadg2997-eadg2997, 2023

PubMed Abstract: The assembly of the autophagy initiation machinery nucleates autophagosome biogenesis, including in the PINK1- and Parkin-dependent mitophagy pathway implicated in Parkinson's disease. The structural interaction between the sole transmembrane autophagy protein, autophagy-related protein 9A (ATG9A), and components of the Unc-51-like autophagy activating kinase (ULK1) complex is one of the major missing links needed to complete a structural map of autophagy initiation. We determined the 2.4-Å x-ray crystallographic structure of the ternary structure of ATG9A carboxyl-terminal tail bound to the ATG13:ATG101 Hop1/Rev7/Mad2 (HORMA) dimer, which is part of the ULK1 complex. We term the interacting portion of the extreme carboxyl-terminal part of the ATG9A tail the "HORMA dimer-interacting region" (HDIR). This structure shows that the HDIR binds to the HORMA domain of ATG101 by β sheet complementation such that the ATG9A tail resides in a deep cleft at the ATG13:ATG101 interface. Disruption of this complex in cells impairs damage-induced PINK1/Parkin mitophagy mediated by the cargo receptor NDP52.

PubMed: 36791199
DOI: 10.1126/sciadv.adg2997

実験手法

X-RAY DIFFRACTION (2.41 Å)