박시훈 (고려대학교, 현 Friedrich Miescher Institute for Biomedical Research)

한빛사 논문

조회320

고려대학교, 현 Friedrich Miescher Institute for Biomedical Research

Nat. Struct. Mol. Biol., Sep 28 2023 | https://doi.org/10.1038/s41594-023-01111-7 Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane.

Si Hoon Park ^1,6, Juhyun Han¹, Byung-Cheon Jeong1^,7, Ju Han Song^1,8, Se Hwan Jang², Hyeongseop Jeong ³, Bong Heon Kim1^, Young-Gyu Ko ¹, Zee-Yong Park², Kyung Eun Lee⁴, Jaekyung Hyun ⁵ & Hyun Kyu Song¹

¹Department of Life Sciences, Korea University, Seoul, South Korea.

²School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, South Korea.

³Center for Electron Microscopy Research, Korea Basic Science Institute, Cheongju-si, South Korea.

⁴Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, South Korea.

⁵School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.

⁶Present address: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

⁷Present address: CSL Seqirus, Waltham, MA, USA.

⁸Present address: Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea.

Corresponding author : Correspondence to Hyun Kyu Song.

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.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-10-01)
연구진국내 연구진
분야 생명과학 > 구조생물 및 생물물리학

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