Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Selective modulation of autophagy is a promising therapeutic strategy, especially for cancer treatment. However, the lack of specific autophagy inhibitors limits this strategy. The formation of the ATG12-ATG5-ATG16L1 complex is essential for targeting the ATG12-ATG5 conjugate to proper membranes and to generate LC3-II for the progression of autophagy. Thus, targeting ATG5-ATG16L1 protein-protein interactions (PPIs) might inhibit early stage autophagy with high specificity. In this paper, we report that a stapled peptide derived from ATG16L1 exhibits potent binding affinity to ATG5, striking resistance to proteolysis, and significant autophagy inhibition activities in cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.2c07648 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ATG16L1 membrane recruitment in autophagy.
Crit Rev Biochem Mol Biol
August 2025
Medical Research Institute, State Key Laboratory of Resource Insects, Southwest University, Chongqing, China.
Autophagy, a highly conserved catabolic pathway in eukaryotes, is essential for cellular survival during starvation and for maintaining cellular homeostasis. Central to autophagy is the formation of double-membrane autophagosomes, which requires the orchestrated action of a set of autophagy-related (ATG) proteins. ATG16L1 is a core autophagy protein involved in distinct phases of autophagosome biogenesis, including membrane remodeling and the formation of phagophore-like membrane cups.
View Article and Find Full Text PDFATG5 is dispensable for ATG8ylation of cellular proteins.
Autophagy Rep
October 2024
University College London, Laboratory for Molecular Cell Biology, London, United Kingdom.
Protein ATG8ylation refers to a post-translational modification involving covalent attachment of ubiquitin-like autophagy-related protein ATG8 (LC3/GABARAP) to other cellular proteins, with reversal mediated by ATG4 proteases. While lipid ATG8ylation is important for autophagosome formation and mechanistically well-characterized, little is known about the mechanism of protein ATG8ylation. Here, we investigated the conjugation machinery of protein ATG8ylation in CRISPR/Cas9-engineered knockout human cell lines, utilizing a deconjugation-resistant (Q116P G120) form of MAP1LC3B.
View Article and Find Full Text PDFTAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance.
Zool Res
July 2024
Translational Research Institute of Henan Provincial People's Hospital and People''s Hospital of Zhengzhou University, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450053, China.
Article Synopsis
- Autophagy is crucial for maintaining and differentiating neural stem cells (NSCs), and while deleting certain genes severely affects these processes, inhibiting canonical autophagy doesn’t have similar detrimental effects.
- Research shows that FIP200 plays a significant role in non-canonical autophagic degradation of p62, primarily through TAX1BP1, which is vital for NSC function.
- The study indicates that targeting the FIP200-TAX1BP1 pathway could offer new therapeutic strategies for neurodegenerative disorders by improving NSC maintenance and function.
Three-step docking by WIPI2, ATG16L1, and ATG3 delivers LC3 to the phagophore.
Sci Adv
February 2024
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
The covalent attachment of ubiquitin-like LC3 proteins (microtubule-associated proteins 1A/1B light chain 3) prepares the autophagic membrane for cargo recruitment. We resolve key steps in LC3 lipidation by combining molecular dynamics simulations and experiments in vitro and in cellulo. We show how the E3-like ligaseautophagy-related 12 (ATG12)-ATG5-ATG16L1 in complex with the E2-like conjugase ATG3 docks LC3 onto the membrane in three steps by (i) the phosphatidylinositol 3-phosphate effector protein WD repeat domain phosphoinositide-interacting protein 2 (WIPI2), (ii) helix α2 of ATG16L1, and (iii) a membrane-interacting surface of ATG3.
View Article and Find Full Text PDFWhat's in an E3: role of highly curved membranes in facilitating LC3-phosphatidylethanolamine conjugation during autophagy.
Autophagy
March 2024
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA, USA.
During autophagosome formation, ATG3, an E2-like enzyme, catalyzes the transfer of LC3-family proteins (including Atg8 in yeast and LC3- and GABARAP-subfamily members in more complex eukaryotes) from the covalent conjugated ATG3-LC3 intermediate to PE lipids in targeted membranes. A recent study has shown that the catalytically important regions of human ATG3 (hereafter referred to as ATG3), including residues 262 to 277 and 291 to 300, in cooperation with its N-terminal curvature-sensing amphipathic helix (NAH), directly interact with the membrane. These membrane interactions are functionally necessary for in vitro conjugation and in vivo cellular assays.
View Article and Find Full Text PDF