Si Hoon Park, Juhyun Han, Byung-Cheon Jeong, Ju Han Song, Se Hwan Jang, Hyeongseop Jeong, Bong Heon Kim, Young-Gyu Ko, Zee-Yong Park, Kyung Eun Lee, Jaekyung Hyun, Hyun Kyu Song
Nature structural & molecular biology 2023 NovDefects 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. © 2023. The Author(s).
Si Hoon Park, Juhyun Han, Byung-Cheon Jeong, Ju Han Song, Se Hwan Jang, Hyeongseop Jeong, Bong Heon Kim, Young-Gyu Ko, Zee-Yong Park, Kyung Eun Lee, Jaekyung Hyun, Hyun Kyu Song. Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane. Nature structural & molecular biology. 2023 Nov;30(11):1695-1706
PMID: 37770719
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