
哺乳類のオートファゾーム形成の開始には、ULK1/2、ATG13、ATG101、FIP200からなるULKコンプレックスが重要な役割を果たす。本研究では、AlphaFold2を用いて予測したULK1-ATG13-FIP200の三者相互作用の構造的基盤を実験的に確認し、この三者相互作用がオートファジー活性化に必須であることを明らかにした。


coremsg

In mammals, autophagosome formation, a central event in autophagy, is initiated by the ULK complex comprising ULK1/2, FIP200, ATG13, and ATG101. However, the structural basis and mechanism of the ULK complex formation remain poorly understood. Here, we predicted the core interactions organizing the ULK complex using AlphaFold, which proposed that the intrinsically disordered region of ATG13 binds to the base of the two UBL domains in the FIP200 dimer using two phenylalanines and to the tandem MIT domain of ULK1, allowing for the 1:1:2 stoichiometry of the ULK1–ATG13–FIP200 complex. We confirmed the predicted interactions by point mutations and revealed the existence of direct triad interactions among ULK1, ATG13, and FIP200 in vitro and in cells, in which each interaction was additively important for autophagic flux. These results indicate that the ULK1–ATG13–FIP200 triadic interaction is crucial for autophagosome formation and provide a structural basis and insights into the regulation mechanism of autophagy initiation in mammals.

### Competing Interest Statement

The authors have declared no competing interest.

The triad interaction of ULK1, ATG13, and FIP200 is required for ULK complex formation and autophagy

哺乳類におけるulk1-atg13-fip200の三者相互作用がulkコンプレックス形成とオートファジーに必要不可欠である


哺乳類におけるULK1、ATG13、FIP200の三者相互作用がULKコンプレックス形成とオートファジーに必要不可欠である
