9C82

Structure of human ULK1C:PI3KC3-C1 supercomplex

This is a non-PDB format compatible entry.

Replaces:  8SRQ

Summary for 9C82

• Entry DOI: 10.2210/pdb9c82/pdb
• Related: 8SOI 8SQZ 8SRM
• EMDB information: 45297
• Descriptor: Phosphoinositide 3-kinase regulatory subunit 4, Phosphatidylinositol 3-kinase catalytic subunit type 3, Beclin 1-associated autophagy-related key regulator, ... (5 entities in total)
• Functional Keywords: autophagy, protein kinase, lipid kinase, supercomplex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 435640.13

Authors

Chen, M.,Hurley, J.H. (deposition date: 2024-06-11, release date: 2024-07-03, Last modification date: 2025-06-18)

Primary citation

Chen, M.,Nguyen, T.N.,Ren, X.,Khuu, G.,Cook, A.S.I.,Zhao, Y.,Yildiz, A.,Lazarou, M.,Hurley, J.H.
Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex.
Nat.Struct.Mol.Biol., 2025

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 autophagy through formation of a ULK1C:PI3KC3-C1 supercomplex and dimerization of ULK1 on the FIP200 scaffold.

PubMed: 40442316
DOI: 10.1038/s41594-025-01557-x

Experimental method

ELECTRON MICROSCOPY (6.84 Å)