Park, Si Hoon Han, Juhyun Jeong, Byung-Cheon Song, Ju Han Jang, Se Hwan Jeong, Hyeongseop Kim, Bong Heon Ko, Young-Gyu Park, Zee-Yong Lee, Kyung Eun Hyun, Jaekyung Song, Hyun Kyu 2024-01-19T08:30:33Z 2024-01-19T08:30:33Z 2023-10-29 2023-11 1545-9993 https://pubs.kist.re.kr/handle/201004/113134 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. The authors present the full-length dimeric TRIM72 E3 ubiquitin ligase and the architecture of its high-order assembly bound to a phosphatidylserine-enriched membrane, providing insights into its role in membrane repair and ubiquitylation. English Nature Publishing Group Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane Article 10.1038/s41594-023-01111-7 1 Nature Structural & Molecular Biology, v.30, no.11, pp.1695 - 1706 Nature Structural & Molecular Biology 30 11 1695 1706 Y scie scopus 001074773600002 2-s2.0-85173011525 Biochemistry & Molecular Biology Biophysics Cell Biology Biochemistry & Molecular Biology Biophysics Cell Biology Article CRYO-EM PROTEIN REPAIR DOMAIN RECOGNITION GENE RESOLUTION REFINEMENT SCATTERING MECHANISM