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Allosteric regulation through a switch element in the autophagy E2, Atg3
- Source :
- Autophagy
- Publication Year :
- 2019
-
Abstract
- Lipidation of Atg8-family ubiquitin-like proteins (UBLs) plays important roles in macroautophagy/autophagy. This process is catalyzed by an E1-E2-E3 trienzyme cascade, in which an E1 enzyme, Atg7, directs Atg8 to its E2 enzyme, Atg3, forming a thioester bond-linked Atg3~ Atg8 intermediate; then the composite E3, Atg12–Atg5-Atg16, interacts with the Atg3~ Atg8 intermediate and promotes Atg8 transfer from the catalytic cysteine of Atg3 to the head group of phosphatidylethanolamine (PE) lipids. Despite progress that has been made toward understanding the Atg8 lipidation pathway, the molecular mechanism of Atg3 as it orchestrates between the E1 and E3 remains unclear. Here we summarize our recent work reporting an element in Atg3, termed the E1, E2, and E3-interacting region (E123IR), is an allosteric switch: in the absence of other binding partners, the E123IR restrains Atg3′s catalytic loop, while the E1 or E3 enzyme directly binds this region to remove this brace and thereby conformationally activate Atg3 to elicit Atg8 lipidation in vitro and in vivo.
- Subjects :
- 0301 basic medicine
chemistry.chemical_classification
030102 biochemistry & molecular biology
ATG8
Allosteric regulation
Autophagy
Autophagy-Related Proteins
Lipid-anchored protein
Cell Biology
Ubiquitin-Activating Enzymes
Biology
Autophagic Punctum
Cell biology
03 medical and health sciences
030104 developmental biology
Enzyme
chemistry
Allosteric Regulation
Ubiquitin-Conjugating Enzymes
Animals
Humans
Molecular Biology
Microtubule-Associated Proteins
Subjects
Details
- ISSN :
- 15548635
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....87beb0d446a0c961f637851d16eef343