{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Duan Y"],"funding":["NINDS NIH HHS"],"pubmed_abstract":["The ULK1 complex (ULK1C) and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) act together to initiate autophagy. Human ULK1C consists of ULK1 itself, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P generated by PI3KC3-C1 is essential to recruit and stabilize ULK1C on membranes for ULK1 to phosphorylate its membrane-associated substrates in autophagy induction, even though ULK1C subunits do not contain any PI3P-binding domains. Here we show that the ATG13:ATG101 dimer forms a tight complex with the PI3P-binding protein WIPI3, as well as with WIPI2. Bound to WIPI2-3, ATG13:ATG101 aligns with the membrane to insert its Trp-Phe (WF) finger into the membrane. Molecular dynamics simulations show that alignment of WIPIs and the ATG101 WF finger cooperatively stabiliz"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.11.07.687251"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12637519"],"repository":["biostudies-literature"],"pubmed_title":["Reconstitution of multistep recruitment of ULK1 to membranes in autophagy."],"pmcid":["PMC12637519"],"funding_grant_id":["R01 NS134598"],"pubmed_authors":["Cook ASI","Ren X","Hurley JH","Martens S","Lu Y","Betz J","Adriaenssens E","Paul S","Wilhelm L","Hummer G","Ganley IG","Duan Y"],"additional_accession":[]},"is_claimable":false,"name":"Reconstitution of multistep recruitment of ULK1 to membranes in autophagy.","description":"The ULK1 complex (ULK1C) and the class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) act together to initiate autophagy. Human ULK1C consists of ULK1 itself, FIP200, and the HORMA domain heterodimer ATG13:ATG101. PI3P generated by PI3KC3-C1 is essential to recruit and stabilize ULK1C on membranes for ULK1 to phosphorylate its membrane-associated substrates in autophagy induction, even though ULK1C subunits do not contain any PI3P-binding domains. Here we show that the ATG13:ATG101 dimer forms a tight complex with the PI3P-binding protein WIPI3, as well as with WIPI2. Bound to WIPI2-3, ATG13:ATG101 aligns with the membrane to insert its Trp-Phe (WF) finger into the membrane. Molecular dynamics simulations show that alignment of WIPIs and the ATG101 WF finger cooperatively stabiliz","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-11T03:12:23.048Z","creation":"2026-06-11T03:08:10.463Z"},"accession":"S-EPMC12637519","cross_references":{"pubmed":["41278708"],"doi":["10.1101/2025.11.07.687251"]}}