Atg16

Atg16 (autophagy-related 16) is a conserved autophagy-related protein first characterized in yeast as part of the core Atg12–Atg5–Atg16 complex that drives autophagosome formation during macroautophagy. In eukaryotes, members of this family participate in the conjugation system that attaches Atg8 family proteins to membranes, a key step in autophagosome biogenesis.

In Saccharomyces cerevisiae, Atg16 forms a stable dimer that binds Atg5–Atg12 and localizes to the pre-autophagosomal structure (PAS). The Atg12–Atg5–Atg16 complex acts as an E3-like cofactor, facilitating the lipidation of Atg8/LC3 family proteins on the expanding phagophore, thereby promoting autophagosome formation.

In mammals, two Atg16 homologs exist: ATG16L1 and ATG16L2. ATG16L1 forms a complex with ATG5–ATG12 and is essential for canonical autophagy and selective autophagy pathways. Genetic variants in ATG16L1, notably the T300A polymorphism, have been associated with increased risk of Crohn's disease and related inflammatory conditions, likely through altered autophagy and innate immunity in intestinal cells. ATG16L2 appears to be less central to core autophagy in most contexts, and its precise functions may include autophagy-related processes or broader vesicular trafficking roles.

Structurally, Atg16/ATG16L proteins contain coiled-coil regions that mediate dimerization and interactions with Atg5, enabling recruitment of the Atg12–Atg5 conjugate to maturing autophagic membranes. Localization is typically to sites of phagophore assembly, and activity is regulated by nutrient signals and upstream autophagy regulators such as mTOR.

Research on yeast and mammals shows ATG16 proteins are central to autophagic flux and selective degradation of pathogens and damaged organelles, with implications for immunity, metabolism, and disease.