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

## TL;DR

This study explores how the coiled-coil domain of TRIM72 helps repair cell membranes by forming flexible structures that tether membranes together.

## Contribution

The study reveals the structural and dynamic role of the coiled-coil domain in TRIM72's membrane repair mechanism.

## Key findings

- The coiled-coil domain of TRIM72 is highly flexible and can move perpendicular to membranes.
- Coiled-coil-mediated oligomerization helps tether adjacent membranes, aiding repair.
- Cryo-electron microscopy showed that TRIM72's coiled-coil domain supports higher-order membrane assembly.

## 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.

Image 1

•TRIM family proteins possess a characteristic hendecad-repeat coiled-coil structure.•The peripheral region of the coiled-coil domain of TRIM exhibits extreme flexibility.•The coiled-coil domain is involved in its oligomerization on the membrane.•The coiled-coil-mediated oligomerization facilitates the tethering of adjacent membranes.

TRIM family proteins possess a characteristic hendecad-repeat coiled-coil structure.

The peripheral region of the coiled-coil domain of TRIM exhibits extreme flexibility.

The coiled-coil domain is involved in its oligomerization on the membrane.

The coiled-coil-mediated oligomerization facilitates the tethering of adjacent membranes.