ArticleNature structural & molecular biology2019
Evolution from covalent conjugation to non-covalent interaction in the ubiquitin-like ATG12 system.
Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- GlRac regulates an ATG8-independent autophagy-like pathway in Giardia lamblia.PLoS pathogens · 2026Article
- Divergent Autophagy Pathways in Plasmodium: Mechanisms, Functions, and Therapeutic Potential.Molecular microbiology · 2026Review
- TRIM38 Suppresses Breast Cancer Progression via Modulating SQSTM1 Ubiquitination and Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Evolutionary diversification of the autophagy initiation complex: reduced Atg101 dependency and changes in Atg9 binding to Atg13.Autophagy · 2025Article
- Keeping your endosymbiont under control: the enigmatic plastid membrane ATG8ylation in Apicomplexa parasites.Autophagy · 2025Article
- CSP ubiquitylation favours Plasmodium berghei survival during early liver stage infection.Scientific reports · 2025Article
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- The relationship between autophagy and respiratory viruses.Archives of microbiology · 2024Review
- A novel fluorescence-activated cell sorting (FACS)-based screening identified ATG14, the gene required for pexophagy in the methylotrophic yeast.FEMS yeast research · 2024Article
- Beclin-1: a therapeutic target at the intersection of autophagy, immunotherapy, and cancer treatment.Frontiers in immunology · 2024Review
- In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases.Frontiers in molecular biosciences · 2024Review
- Autophagy genes in biology and disease.Nature reviews. Genetics · 2023Review
- Apicoplast biogenesis mediated by ATG8 requires the ATG12-ATG5-ATG16L and SNAP29 complexes inAutophagy · 2023Article
- Article
- HSF1 Attenuates the Release of Inflammatory Cytokines Induced by Lipopolysaccharide through Transcriptional Regulation ofMicrobiology spectrum · 2023Article
- Regulation of Mitochondrial Energy Metabolism by Glutaredoxin 5 in the Apicomplexan Parasite Neospora caninum.Microbiology spectrum · 2023Article
- Structural biology of the Atg8 and Atg12 conjugation systems.Autophagy reports · 2023Review
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Evolutionary diversification of the autophagy-related ubiquitin-like conjugation systems.Autophagy · 2022Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.