Role of N-glycosylation as a determinant of ATG9A conformations and activity.

ABSTRACT: Here, we investigate the effects of glycosylation at position N99 on the structural dynamics and lipid scrambling activity of ATG9A, a key autophagy protein, using microsecond all-atom molecular dynamics simulations. ATG9A is an integral membrane protein involved in autophagosome biogenesis, and glycosylation at N99 has previously been implicated in intracellular trafficking, although its precise role remains unclear. The simulations reveal that the hydrophilic central cavity of ATG9A supports lipid reorientation and partial trans-bilayer movements, consistent with experiments on its lipid scrambling activity. We propose that N-glycosylation at N99 enhances cooperative interactions between protomers, facilitating lipid insertion and translocation within the central cavity. These findings s

SUBMITTER: Utichi M 

PROVIDER: S-EPMC12743292 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature