{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen M"],"funding":["NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["1596-1605"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12440827"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(9)"],"pubmed_abstract":["The Unc-51-like kinase protein kinase complex (ULK1C) is the most upstream and central player in the initiation of macroautophagy in mammals. Here, we determined the cryo-electron microscopy structure of the human ULK1C core at amino-acid-level resolution. We also determined a moderate-resolution structure of the ULK1C core in complex with another autophagy core complex, the class III phosphatidylinositol 3-OH kinase complex I (PI3KC3-C1). We show that the two complexes coassemble through extensive contacts between the FIP200 scaffold subunit of ULK1C and the VPS15, ATG14 and BECN1 subunits of PI3KC3-C1. The FIP200:ATG13:ULK1 core of ULK1C undergoes a rearrangement from 2:1:1 to 2:2:2 stoichiometry in the presence of PI3KC3-C1. This suggests a structural mechanism for the initiation of aut"],"journal":["Nature structural & molecular biology"],"pubmed_title":["Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex."],"pmcid":["PMC12440827"],"funding_grant_id":["R35 GM136414","R01 NS134598"],"pubmed_authors":["Ren X","Cook ASI","Lazarou M","Hurley JH","Chen M","Nguyen TN","Zhao Y","Khuu G","Yildiz A"],"additional_accession":[]},"is_claimable":false,"name":"Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex.","description":"The Unc-51-like kinase protein kinase complex (ULK1C) is the most upstream and central player in the initiation of macroautophagy in mammals. Here, we determined the cryo-electron microscopy structure of the human ULK1C core at amino-acid-level resolution. We also determined a moderate-resolution structure of the ULK1C core in complex with another autophagy core complex, the class III phosphatidylinositol 3-OH kinase complex I (PI3KC3-C1). We show that the two complexes coassemble through extensive contacts between the FIP200 scaffold subunit of ULK1C and the VPS15, ATG14 and BECN1 subunits of PI3KC3-C1. The FIP200:ATG13:ULK1 core of ULK1C undergoes a rearrangement from 2:1:1 to 2:2:2 stoichiometry in the presence of PI3KC3-C1. This suggests a structural mechanism for the initiation of aut","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T08:00:57.535Z","creation":"2026-04-26T03:12:05.58Z"},"accession":"S-EPMC12440827","cross_references":{"pubmed":["40442316"],"doi":["10.1038/s41594-025-01557-x"]}}