Insights into the membrane repair mechanism by the coiled-coil-mediated oligomerization of TRIM72

Si Hoon Park; Georg Kempf; Hyun Kyu Song

doi:10.1016/j.bbrep.2025.102308

Insights into the membrane repair mechanism by the coiled-coil-mediated oligomerization of TRIM72

Biochem Biophys Rep. 2025 Oct 12:44:102308. doi: 10.1016/j.bbrep.2025.102308. eCollection 2025 Dec.

Authors

Si Hoon Park^{1

2}, Georg Kempf², Hyun Kyu Song¹

Affiliations

¹ Department of Life Sciences, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea.
² Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel, 4056, Switzerland.

Abstract

TRIpartite Motif-containing 72 (TRIM72, also known as MG53), a RING-type E3 ubiquitin ligase, is critical for plasma membrane repair. Like other TRIM family proteins, TRIM72 has a conserved architecture comprising RING, B-box, coiled-coil, and C-terminal PRY-SPRY domains. While the coiled-coil domain mediates homo-oligomerization, its specific contribution to the membrane repair machinery remains unclear. In this study, we characterized the structural and dynamic properties of the TRIM72 coiled-coil domain, aiming to elucidate its contribution to membrane association. Small-angle X-ray scattering and molecular dynamics simulations revealed that the coiled-coil domain exhibits significant flexibility, including directional movements perpendicular to the membrane. Cryo-electron microscopy further demonstrated that coiled-coil-mediated oligomerization facilitated the tethering of adjacent liposomes. These findings highlight the role of the coiled-coil domain in supporting higher-order assembly on membranes, providing mechanistic insights into the TRIM72-mediated membrane repair.

Keywords: Coiled-coil; E3 ubiquitin ligase; Hendecad repeat; MG53; Membrane curvature; Oligomerization; TRIM72.