Shen et al. reveal how a key portion of the membrane-snipping ESCRT-III complex gets in shape.
The ESCRT-III complex cuts membranes during processes such as cell division and viral budding. The complex contains several subunits, the most abundant of which is Vps32 (known as CHMP4 in mammals). How the different subunits coalesce to produce a full-fledged ESCRT-III complex remains unclear. Researchers have found that Vps32 subunits often polymerize into a flat spiral that could be the foundation on which the rest of the complex assembles.
Shen et al. used cryo-EM and other techniques to probe the architecture of the Vps32 coils. The team found that they form spontaneously when Vps32 proteins link up. The subunits, which line up end to end rather than side by side, are well suited to adopt a bowed conformation. Two of the helices in the Vps32 structure have a hinge in the middle. When the team mutated this hinge, the proteins could no longer form spirals. The researchers calculated that the most energetically favorable curvature for the subunits was 9°, and they found that the proteins in the center of the spirals bend at almost exactly that angle.
In contrast, Shen et al. discovered that the junctions between Vps32 subunits are stiff, suggesting that bending there doesn’t contribute to the spiral shape. The bulky carboxyl terminus of Vps32 prevents other Vps32 proteins from sidling up to the filaments, and the authors found that a downstream ESCRT-III component, the Vps4 ATPase, helps tighten the spiral in a way that doesn’t require ATP hydrolysis.
The results suggest that the Vps32 spirals might function like a coiled spring, storing energy that can be used to cut membranes.
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Text by Mitch Leslie
