7XV2

TRIM E3 ubiquitin ligase

Summary for 7XV2

• Entry DOI: 10.2210/pdb7xv2/pdb
• Descriptor: Tripartite motif-containing protein 72, ZINC ION (2 entities in total)
• Functional Keywords: trim, tripartite motif, ubiquitin ligase, coiled coil, b-box, pry-spry, membrane protein, ligase, metal binding protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 44331.34

Authors

Park, S.H.,Song, H.K. (deposition date: 2022-05-20, release date: 2023-05-24, Last modification date: 2023-11-29)

Primary citation

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.
Structure and activation of the RING E3 ubiquitin ligase TRIM72 on the membrane.
Nat.Struct.Mol.Biol., 30:1695-1706, 2023

PubMed 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.

PubMed: 37770719
DOI: 10.1038/s41594-023-01111-7

Experimental method

X-RAY DIFFRACTION (2.75 Å)