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Autophagic Punctum

The ingenious ULKs: expanding the repertoire of the ULK complex with phosphoproteomics

& ORCID Icon
Pages 4491-4493 | Received 30 Jul 2021, Accepted 11 Aug 2021, Published online: 14 Sep 2021

Figures & data

Figure 1. ULK regulates PtdIns3K activity by phosphorylating PIK3R4/VPS15. (A) Human PtdIns3K complex II with PIK3C3/VPS34 (gray), PIK3R4/VPS15 (green), BECN1 (beige) and UVRAG (pink).. PIK3R4/VPS15 domains are labeled in green. ULK phosphorylates PIK3R4/VPS15 at 6 sites, the major phosphoacceptor is serine 861. Phosphorylation promotes lipid kinase activity, omegasome formation and autophagic flux. (B) PIK3R4/VPS15 structural prediction from AlphaFold Protein Structural Database (see https://alphafold.ebi.ac.uk/entry/Q99570). Color indicates model confidence (navy = very high; aqua = confident; yellow = low; orange = very low). Serine 861 lies in the unstructured linker region connecting the HEAT and WD40 domains. The red dashed box indicates the region surrounding serine 861, which is magnified on the left hand side. Blue dashed lines indicate hydrogen bonds stabilizing the alpha helix

Figure 1. ULK regulates PtdIns3K activity by phosphorylating PIK3R4/VPS15. (A) Human PtdIns3K complex II with PIK3C3/VPS34 (gray), PIK3R4/VPS15 (green), BECN1 (beige) and UVRAG (pink).. PIK3R4/VPS15 domains are labeled in green. ULK phosphorylates PIK3R4/VPS15 at 6 sites, the major phosphoacceptor is serine 861. Phosphorylation promotes lipid kinase activity, omegasome formation and autophagic flux. (B) PIK3R4/VPS15 structural prediction from AlphaFold Protein Structural Database (see https://alphafold.ebi.ac.uk/entry/Q99570). Color indicates model confidence (navy = very high; aqua = confident; yellow = low; orange = very low). Serine 861 lies in the unstructured linker region connecting the HEAT and WD40 domains. The red dashed box indicates the region surrounding serine 861, which is magnified on the left hand side. Blue dashed lines indicate hydrogen bonds stabilizing the alpha helix