ATG2AB

ATG2AB refers to two closely related autophagy-related proteins in mammals, ATG2A and ATG2B, which are homologs of the yeast Atg2. They are large, coiled-coil proteins that function in macroautophagy, particularly in phagophore membrane expansion and autophagosome formation.

Function and mechanism: ATG2A and ATG2B act as lipid transfer and tethering factors that facilitate delivery of lipids to the growing phagophore from donor membranes such as the endoplasmic reticulum. They are proposed to bridge membranes and coordinate lipid supply during autophagosome biogenesis, supporting efficient LC3 lipidation and maturation of autophagosomes.

Localization and interactions: Both proteins localize to autophagosome precursors and ER–phagophore contact sites. They interact with ATG9A and with PI3P effectors such as WIPI2 and WIPI4, which assist in membrane recruitment. The C-terminal region of ATG2 proteins interacts with WIPI4, while the N-terminal portion contributes to membrane associations, consistent with a membrane-bridging tether model.

Genetics and redundancy: ATG2A and ATG2B are vertebrate paralogs with overlapping roles in autophagy. Depletion of either protein reduces autophagic flux in cells, and dual disruption produces stronger defects in autophagosome formation, indicating functional redundancy in the pathway.

Structure: Both proteins are predicted to be elongated, coiled-coil molecules with distinct N- and C-terminal regions implicated in lipid handling and protein interactions. Structural analyses support a long, rod-like conformation compatible with a membrane-bridging function.

Clinical relevance: Because of their central role in autophagy, ATG2A and ATG2B are studied in the context of diseases associated with autophagy dysregulation, including cancer and neurodegenerative conditions, though specific disease associations require further elucidation.