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TitleAtg9 is a lipid scramblase that mediates autophagosomal membrane expansion.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 12, Page 1185-1193, Year 2020
Publish dateOct 26, 2020
AuthorsKazuaki 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 AbstractThe 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.
External linksNat Struct Mol Biol / PubMed:33106658
MethodsEM (single particle)
Resolution3.0 - 4.7 Å
Structure data

30535

7d0i

EMDB-30535, PDB-7d0i:
Cryo-EM structure of Schizosaccharomyces pombe Atg9
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-30545:
Cryo-EM structure of Schizosaccharomyces pombe Atg9 of trimer
Method: EM (single particle) / Resolution: 4.7 Å

Chemicals

ChemComp-LMN:
Lauryl Maltose Neopentyl Glycol / detergent*YM

Source
  • schizosaccharomyces pombe (strain 972 / atcc 24843) (yeast)
  • Schizosaccharomyces pombe (fission yeast)
KeywordsUNKNOWN FUNCTION / Autophagy / membrane protein

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