9t0c | pdb_00009t0c

Atg2-Atg18 complex from yeast

spinqualitylabelsall models 9t0c, resolution 4.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9t0c is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ATG2_YEAST Lipid transfer protein required for autophagosome completion and peroxisome degradation (PubMed:10029994, PubMed:11382760, PubMed:11382761, PubMed:11675007, PubMed:18586673, PubMed:18625846, PubMed:19371383, PubMed:19995911, PubMed:22728243, PubMed:23230146, PubMed:8224160). Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion (PubMed:28704456, PubMed:29848619, PubMed:30254161). ATG2 binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, using basic residues in its N-terminal region (NR) and to the expanding edge of the IM through its C-terminal region (PubMed:30254161). The latter binding is assisted by an ATG18-PtdIns3P interaction (PubMed:30254161). ATG2 then extracts phospholipids from the membrane source using its NR and transfers them to ATG9 to the IM through its predicted beta-sheet-rich structure for membrane expansion (PubMed:30254161). ATG2 is also involved in the recruitment of lipids to a restricted region close to the vacuole, termed the vacuole-isolation membrane contact site (VICS), which is also essential for autophagosome formation (PubMed:28704456). Necessary for the localization of ATG18 to the preautophagosomal structure (PAS) and the binding of ATG18 to ATG9 (PubMed:14723849, PubMed:18586673, PubMed:18625846, PubMed:19371383, PubMed:23230146). ATG2 is the most downstream ATG protein in the preautophagosomal structure organization process (PubMed:17295840). Involved in correct ATG9 trafficking through the preautophagosomal structure and in peroxisome degradation (PubMed:14723849). Plays a significant role in life span extension (PubMed:23337777). Publication Abstract from PubMed During macroautophagy, the de novo formation of the autophagosome at a membrane contact site (MCS) with the endoplasmic reticulum requires directional lipid flux for the growth of the initial phagophore before its sealing into an autophagosome and subsequent fusion with the lysosome/vacuole. It remains unclear, however, how the formation of this specialized MCS and the directionality of the lipid flux are controlled. Here, we present the structure of the key lipid transfer protein Atg2 from yeast solved together with its Atg18 binding partner, a phosphatidylinositol-3-phosphate (PtdIns3P) effector, using cryo-electron microscopy. We reveal a new interface in Atg2 that, together with PtdIns3P, is required for Atg18 recruitment and lipid transfer activity. Furthermore, we visualize lipid densities along the internal hydrophobic cavity of Atg2, providing structural evidence that Atg2 cavity is filled with lipids throughout the entire length, even when Atg2 is cytosolic. Finally, molecular dynamics simulations show that the complex generates membrane curvature, efficiently positioning the lipid channel of Atg2 towards the membrane to promote lipid transfer into the elongating phagophore. Atg18 interaction positions Atg2 for efficient lipid transfer into phagophore elongation.,Ramirez SC, Shvarev D, Vargas Duarte P, Ahmed Y, Milach J, Lang E, Kuchenbuch S, Vanni S, Reggiori F, Moeller A, Ungermann C EMBO J. 2026 May 20. doi: 10.1038/s44318-026-00802-3. PMID:42162239 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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