The WIPI homolog Atg18 binds to and tethers membranes containing phosphatidylinositol-3,4,5-triphosphate.
Noguera-Canas, F. L.; Diaz-Agustin, A.; Gavira, J. A.; Paredes, J. M.; Salto, R.; Orte, A.; Conejero-Lara, F.; Martin-Martinez, M.; Perez-Lara, F. A.
Show abstract
Atg18 --for Autophagy-related gene 18-- is a member of the PROPPIN ({beta}-propellers that bind polyphosphoinositides) family, which is known for its binding to phosphorylated phosphoinositides through two conserved binding sites. Although Atg18 binding to polyphosphoinositides is crucial for its roles in both autophagic and non-autophagic functions within cells, the precise molecular mechanism by which Atg18 selectively binds to specific phosphatidylinositols remains unresolved. Here, we combined molecular dynamic simulations and biophysical methods --including isothermal titration calorimetry (ITC), cosedimentation, fluorescence resonance energy transfer (FRET), and dynamic light scattering (DLS)-- to characterize the interaction between Atg18 and polyphosphoinositides. In contrast to previous findings, we demonstrate that Atg18 binds to and clusters liposomes containing phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3), suggesting that Atg18 oligomerizes and tethers opposing membranes containing this physiological phosphatidylinositol. Hence, our results provide new insights into how Atg18 and its mammalian homologs, WIPI --for WD-repeat domain phosphoinositide-interacting-- proteins, may regulate organelle membrane organization and vesicle trafficking required for both autophagic and non-autophagic functions.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Cis-membrane association of human ATG8 proteins N-terminus mediates autophagy 94%
- Conformational dynamics and target-dependent myristoyl switch of calcineurin B homologous protein 3 94%
- Periprotein lipidomes of Saccharomyces cerevisiae provide a flexible environment for conformational changes of membrane proteins 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.