8POE

Structure of tissue-specific lipid scramblase ATG9B homotrimer, refined with C3 symmetry applied

8POE の概要

• エントリーDOI: 10.2210/pdb8poe/pdb
• EMDBエントリー: 17789
• 分子名称: Autophagy-related protein 9B (1 entity in total)
• 機能のキーワード: membrane protein, lipid scramblase, autophagy, phagopore, lipid transporter, atg9, atg9b, lipid transport
• 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: 317001.02

構造登録者

Chiduza, G.N.,Pye, V.E.,Tooze, S.A.,Cherepanov, P. (登録日: 2023-07-04, 公開日: 2023-11-15, 最終更新日: 2024-03-20)

主引用文献

Chiduza, G.N.,Garza-Garcia, A.,Almacellas, E.,De Tito, S.,Pye, V.E.,van Vliet, A.R.,Cherepanov, P.,Tooze, S.A.
ATG9B is a tissue-specific homotrimeric lipid scramblase that can compensate for ATG9A.
Autophagy, 20:557-576, 2024

PubMed Abstract: Macroautophagy/autophagy is a fundamental aspect of eukaryotic biology, and the autophay-related protein ATG9A is part of the core machinery facilitating this process. In addition to ATG9A vertebrates encode ATG9B, a poorly characterized paralog expressed in a subset of tissues. Herein, we characterize the structure of human ATG9B revealing the conserved homotrimeric quaternary structure and explore the conformational dynamics of the protein. Consistent with the experimental structure and computational chemistry, we establish that ATG9B is a functional lipid scramblase. We show that ATG9B can compensate for the absence of ATG9A in starvation-induced autophagy displaying similar subcellular trafficking and steady-state localization. Finally, we demonstrate that ATG9B can form a heteromeric complex with ATG2A. By establishing the molecular structure and function of ATG9B, our results inform the exploration of niche roles for autophagy machinery in more complex eukaryotes and reveal insights relevant across species. ATG: autophagy related; CHS: cholesteryl hemisuccinate; cryo-EM: single-particle cryogenic electron microscopy; CTF: contrast transfer function: CTH: C- terminal α helix; FSC: fourier shell correlation; HDIR: HORMA domain interacting region; LMNG: lauryl maltose neopentyl glycol; MD: molecular dynamics simulations; MSA: multiple sequence alignment; NBD-PE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl ammonium salt); POPC: palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; RBG: repeating beta groove domain; RMSD: root mean square deviation; SEC: size-exclusion chromatography; TMH: transmembrane helix.

PubMed: 37938170
DOI: 10.1080/15548627.2023.2275905

実験手法

ELECTRON MICROSCOPY (4.2 Å)