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Evolution from covalent conjugation to non-covalent interaction in the ubiquitin-like ATG12 system.
- Source :
-
Nature structural & molecular biology [Nat Struct Mol Biol] 2019 Apr; Vol. 26 (4), pp. 289-296. Date of Electronic Publication: 2019 Mar 25. - Publication Year :
- 2019
-
Abstract
- Ubiquitin or ubiquitin-like proteins can be covalently conjugated to multiple proteins that do not necessarily have binding interfaces. Here, we show that an evolutionary transition from covalent conjugation to non-covalent interaction has occurred in the ubiquitin-like autophagy-related 12 (ATG12) conjugation system. ATG12 is covalently conjugated to its sole substrate, ATG5, by a ubiquitylation-like mechanism. However, the apicomplexan parasites Plasmodium and Toxoplasma and some yeast species such as Komagataella phaffii (previously Pichia pastoris) lack the E2-like enzyme ATG10 and the most carboxy (C)-terminal glycine of ATG12, both of which are required for covalent linkage. Instead, ATG12 in these organisms forms a non-covalent complex with ATG5. This non-covalent ATG12-ATG5 complex retains the ability to facilitate ATG8-phosphatidylethanolamine conjugation. These results suggest that ubiquitin-like covalent conjugation can evolve to a simpler non-covalent interaction, most probably when the system has a limited number of targets.
- Subjects :
- Animals
Autophagosomes ultrastructure
Autophagy-Related Proteins chemistry
Carrier Proteins chemistry
Carrier Proteins metabolism
Crystallography, X-Ray
Endoplasmic Reticulum ultrastructure
Humans
Liposomes chemistry
Liposomes metabolism
Liposomes ultrastructure
Mice
Mutation
Phospholipids chemistry
Phospholipids metabolism
Schizosaccharomyces metabolism
Schizosaccharomyces ultrastructure
Ubiquitins chemistry
Ubiquitins metabolism
Autophagosomes metabolism
Autophagy-Related Proteins metabolism
Endoplasmic Reticulum metabolism
Membranes metabolism
Membranes ultrastructure
Ubiquitin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1545-9985
- Volume :
- 26
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nature structural & molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 30911187
- Full Text :
- https://doi.org/10.1038/s41594-019-0204-3