Details

Autor(en) / Beteiligte

• 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

Titel

Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane

Ist Teil von

• Nature structural & molecular biology, 2023-11, Vol.30 (11), p.1695-1706

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.