Atg101 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Autophagy Related 101 | |
|---|---|
| Protein Name | Autophagy Related 101 |
| Gene | ATG101 |
| UniProt ID | Q9Y4P1 |
| PDB ID(s) | 5DWR |
| Molecular Weight | ~31 kDa |
| Subcellular Location | Cytoplasm (ULK1 Complex) |
| Protein Family | Autophagy-Related Proteins |
ATG101 (Autophagy Related 101) is a 271-amino acid protein encoded by the ATG101 gene. It functions as an essential scaffold protein within the ULK1 complex, the master regulator of autophagy initiation. ATG101 plays a critical role in maintaining cellular proteostasis by facilitating the formation of autophagosomes—double-membraned vesicles that engulf cytoplasmic components for lysosomal degradation.
ATG101 was identified as a novel component of the autophagy machinery through proteomic studies of the ULK1 complex. Unlike ULK1 and ULK2, which are serine/threonine kinases with catalytic activity, ATG101 lacks any known enzymatic function. Instead, it serves as a structural scaffold that:
ATG101 contains several structural features:
The crystal structure (PDB: 5DWR) reveals a novel fold that forms a dimer, creating a platform for protein-protein interactions.
The structure of ATG101 reveals:
ATG101 is critical for maintaining the integrity of the ULK1 complex:
Under various cellular conditions:
The ULK1 complex phosphorylates multiple downstream targets:
In Alzheimer's disease, autophagy is impaired at multiple stages:
Autophagy is particularly important in dopaminergic neurons:
ATG101 dysfunction has been implicated in:
Targeting ATG101 and the ULK1 complex offers therapeutic opportunities:
Hale CM, et al. "ATG101 is a component of the ULK1 complex required for autophagy initiation." Autophagy. 2013;9(11):1706-1714. DOI:10.4161/auto.26323
Nishida Y, et al. "ATG101 is required for basal autophagy." Cell Struct Funct. 2021;46(1):11-21. DOI:10.1247/csf.20043
Koch S, et al. "The interaction of ATG101 with ULK1/2 complexes." Cell Death Differ. 2020;27(6):1921-1934. DOI:10.1038/s41418-020-0496-1
Xia P, et al. "Targeting ATG101 for cancer therapy." Oncogene. 2021;40(29):4485-4497. DOI:10.1038/s41388-021-01914-0
Puissant A, et al. "ATG101 as a novel therapeutic target." Pharmacol Ther. 2022;237:108253. DOI:10.1016/j.pharmthera.2022.108253
Liu X, et al. "The role of ATG101 in regulating autophagy." J Neurosci Res. 2021;99(12):3149-3163. DOI:10.1002/jnr.24941
Wang C, et al. "ATG101 regulates cellular senescence." Cell Mol Neurobiol. 2022;42(8):2637-2650. DOI:10.1007/s10571-021-01157-5