UC Berkeley

Key PointsEndosomal sorting complex required for transport (ESCRT) proteins carry out scission of membrane necks with a topology (or sidedness) opposite to that of the better-understood process carried out by coat proteins, dynamin and BAR (Bin, amphiphysin and Rvs) domain proteins.ESCRT-mediated reverse-topology membrane scission is initiated by two upstream branches: the first comprising ESCRT-I and ESCRT-II, and the second comprising ALIX.The ESCRT-III protein family has 12 different subunits in humans. ESCRT-III monomers are about 200 amino acids in length and have open and closed conformations.ESCRT-III proteins can assemble into flat spirals, helical tubes or conical funnels.ESCRT-III assemblies are taken apart by the AAA+ ATPase vacuolar protein sorting-associated 4 (VPS4), which unfolds ESCRT-III monomers and threads them through a central pore of the VPS4 hexamer.It is currently unresolved whether scission is mediated by the drawing-together of membrane necks by a tapered dome, buckling by the mechanical spring-like action of curved ESCRT filaments or some other means.