7d0i | pdb_00007d0i
Cryo-EM structure of Schizosaccharomyces pombe Atg9
Structural highlights
Function[ATG9_SCHPO] Involved in autophagy and cytoplasm to vacuole transport (Cvt) vesicle formation. Plays a key role in the organization of the preautophagosomal structure/phagophore assembly site (PAS), the nucleating site for formation of the sequestering vesicle. Required for mitophagy. Cycles between the PAS and the cytoplasmic vesicle pool and may participate in supplying membrane for the growing autophagosome. Also involved in endoplasmic reticulum-specific autophagic process and is essential for the survival of cells subjected to severe ER stress. Different machineries are required for anterograde trafficking to the PAS during either the Cvt pathway or bulk autophagy and for retrograde trafficking (By similarity). Has a role in meiosis and sporulation.[UniProtKB:Q12142][1] Publication Abstract from PubMedThe 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. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion.,Matoba K, Kotani T, Tsutsumi A, Tsuji T, Mori T, Noshiro D, Sugita Y, Nomura N, Iwata S, Ohsumi Y, Fujimoto T, Nakatogawa H, Kikkawa M, Noda NN Nat Struct Mol Biol. 2020 Oct 26. pii: 10.1038/s41594-020-00518-w. doi:, 10.1038/s41594-020-00518-w. PMID:33106658[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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