Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane
Open accessPublished version of a preprint
Abstract
Defects in plasma membrane repair can lead to muscle and heart diseases in humans. Tripartite motif-containing protein (TRIM)72 (mitsugumin 53; MG53) has been determined to rapidly nucleate vesicles at the site of membrane damage, but the underlying molecular mechanisms remain poorly understood. Here we present the structure of Mus musculus TRIM72, a complete model of a TRIM E3 ubiquitin ligase. We demonstrated that the interaction between TRIM72 and phosphatidylserine-enriched membranes is necessary for its oligomeric assembly and ubiquitination activity. Using cryogenic electron tomography and subtomogram averaging, we elucidated a higher-order model of TRIM72 assembly on the phospholipid bilayer. Combining structural and biochemical techniques, we developed a working molecular model of TRIM72, providing insights into the regulation of RING-type E3 ligases through the cooperation of multiple domains in higher-order assemblies. Our findings establish a fundamental basis for the study of TRIM E3 ligases and have therapeutic implications for diseases associated with membrane repair.
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Cites
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ColabFold - Making protein folding accessible to all
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- Authors
- Park, S. H., Han, J., Jeong, B.-C., Song, J. H., Jang, S. H., Jeong, H., Kim, B. H., Ko, Y.-G., Park, Z.-Y., Lee, K. E., Hyun, J., & Song, H. K.
- Affiliations
- Korea University (KR)
- Chonnam National University (KR)
- Gwangju Institute of Science and Technology (KR)
- Korea Basic Science Institute (KR)
- Korea Institute of Science and Technology (KR)
- Sungkyunkwan University (KR)
- Corresponding author
- Song, Hyun Kyu
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2023-09-28
- Volume
- 30
- Issue
- 11
- Pages
- 1695-1706
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC10643145
- OpenAlex
- W4387130457
- Cited by
- 31
- References
- 5
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 9
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-10-28)
- Open access
- hybrid
- doi.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Friedrich Miescher Institute for Biomedical Research
- National Research Foundation
- Korea Basic Science Institute
- National Research Foundation of Korea (2022M3A9G8082638, 2021M3A9I4030068, 2020R1A2C3008285)
- Institute for Protein Research, Osaka University (ICR-21-05, ICR-20-05)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- TRIM72, MG53, RING E3 ubiquitin ligase, plasma membrane repair, oligomeric assembly, ubiquitination, cryo-electron tomography, subtomogram averaging, protein-membrane interactions
- MeSH terms
- Tripartite Motif Proteins, Animals, Heart Diseases, Humans, Membrane Proteins, Models, Molecular, Ubiquitin-Protein Ligases, Mice, Ubiquitination
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