The endosomal protein complex required for transport-III (ESCRT-III) proteins form membrane-remodeling (hetero)polymeric filaments, but how exactly they deform and mediate the fission of lipid membranes is unknown.
ESCRT-III subunits adopt different conformations that polymerize into filaments with distinct polymer architectures.
Depending on their subunit composition, ESCRT-III filaments display different shape parameters (curvature, torsion, rigidity) and different interfaces for protein–protein and protein–membrane interactions.
Lateral interactions of two or more strands of different ESCRT-III homo- or heterofilaments affect overall filament shape parameters.
Dynamic remodeling of ESCRT-III polymers by the AAA ATPase Vps4 can lead to changes in filament shapes and membrane interaction over time, converting the filament from one composition to another.
Endosomal protein complex required for transport-III (ESCRT-III) polymers are involved in many crucial cellular functions, from cell division to endosome–lysosome dynamics. As a eukaryotic membrane remodeling machinery, ESCRT-III is unique in its ability to catalyze fission of membrane necks from their luminal side and to participate in membrane remodeling processes of essentially all cellular organelles. Found in Archaea, it is also the most evolutionary ancient membrane remodeling machinery. The simple protein structure shared by all of its subunits assembles into a large variety of filament shapes, limiting our understanding of how these filaments achieve membrane remodeling. Here, we review recent findings that discovered unpredicted properties of ESCRT-III polymers, which enable us to define general principles of the mechanism by which ESCRT-III filaments remodel membranes.
