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-Structure paper
| タイトル | Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex. |
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| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 32, Issue 9, Page 1596-1605, Year 2025 |
| 掲載日 | 2025年5月29日 |
著者 | Minghao Chen / Thanh N Nguyen / Xuefeng Ren / Grace Khuu / Annan S I Cook / Yuanchang Zhao / Ahmet Yildiz / Michael Lazarou / James H Hurley / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:40442316 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.26 - 6.84 Å |
| 構造データ | ![]() EMDB-41051: Local refinement map (1/3) of the human ULK1 complex core (EMD-40658) ![]() EMDB-41052: Consensus map of the human ULK1 complex core (EMD-40658) ![]() EMDB-41053: Local refinement map (2/3) of the human ULK1 complex core (EMD-40658) ![]() EMDB-41054: Local refinement map (3/3) of the human ULK1 complex core (EMD-40658) ![]() EMDB-41055: Consensus map of the human PI3KC3-C1 complex (EMD-40669) ![]() EMDB-41056: Local refinement map (1/2) of the human PI3KC3-C1 complex (EMD-40669) ![]() EMDB-41057: Local refinement map (2/2) of the human PI3KC3-C1 complex (EMD-40669) EMDB-45297, PDB-9c82: |
| 由来 |
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キーワード | IMMUNE SYSTEM / Autophagy / Protein kinase / Lipid kinase / Supercomplex |
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homo sapiens (ヒト)
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