+検索条件
-Structure paper
タイトル | Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. |
---|---|
ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 12, Page 1185-1193, Year 2020 |
掲載日 | 2020年10月26日 |
著者 | Kazuaki Matoba / Tetsuya Kotani / Akihisa Tsutsumi / Takuma Tsuji / Takaharu Mori / Daisuke Noshiro / Yuji Sugita / Norimichi Nomura / So Iwata / Yoshinori Ohsumi / Toyoshi Fujimoto / Hitoshi Nakatogawa / Masahide Kikkawa / Nobuo N Noda / |
PubMed 要旨 | The molecular function of Atg9, the sole transmembrane protein in the autophagosome-forming machinery, remains unknown. Atg9 colocalizes with Atg2 at the expanding edge of the isolation membrane (IM) ...The molecular function of Atg9, the sole transmembrane protein in the autophagosome-forming machinery, remains unknown. Atg9 colocalizes with Atg2 at the expanding edge of the isolation membrane (IM), where Atg2 receives phospholipids from the endoplasmic reticulum (ER). Here we report that yeast and human Atg9 are lipid scramblases that translocate phospholipids between outer and inner leaflets of liposomes in vitro. Cryo-EM of fission yeast Atg9 reveals a homotrimer, with two connected pores forming a path between the two membrane leaflets: one pore, located at a protomer, opens laterally to the cytoplasmic leaflet; the other, at the trimer center, traverses the membrane vertically. Mutation of residues lining the pores impaired IM expansion and autophagy activity in yeast and abolished Atg9's ability to transport phospholipids between liposome leaflets. These results suggest that phospholipids delivered by Atg2 are translocated from the cytoplasmic to the luminal leaflet by Atg9, thereby driving autophagosomal membrane expansion. |
リンク | Nat Struct Mol Biol / PubMed:33106658 |
手法 | EM (単粒子) |
解像度 | 3.0 - 4.7 Å |
構造データ | EMDB-30535, PDB-7d0i: EMDB-30545: |
化合物 | ChemComp-LMN: |
由来 |
|
キーワード | UNKNOWN FUNCTION / Autophagy / membrane protein |