Molecular Insights into IM30 Folding-Unfolding Transition and Condensate Formation

IM30 is a cyanobacterial ESCRT-III protein essential for membrane stabilization, repair, and remodeling. Like other ESCRT-III members, it forms large oligomers with a conserved structural core flanked by flexible regions that support dynamic function. In addition to oligomerization, IM30 exhibits salt-dependent phase separation, a hallmark of polyampholytes. Here, we combine molecular dynamics simulations with experiments to investigate the molecular principles underlying IM30’s helical dynamics and phase behavior using coarse-grained models. Simulations across different salt concentrations and temperatures enabled the construction of 2D and 3D phase diagrams outlining the conditions for condensate formation, while contact analysis reveals that the N-terminal and coiled-coil regions drive condensate formation, whereas the C-terminal region alone is insufficient. Together, these findings provide a mechanistic framework linking IM30’s structural flexibility, oligomerization, and phase separation to its role in membrane stabilization and repair.