Structure and membrane remodeling activity of ESCRT-III helical polymers

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Science  18 Dec 2015:
Vol. 350, Issue 6267, pp. 1548-1551
DOI: 10.1126/science.aad8305

ESCRTs work in two very different ways

The so-called ESCRT proteins are involved in the budding of vesicles into the lumen of endosomes and in virus budding. These reactions involve the formation of a cytoplasm-filled neck that spirals of the ESCRTs help to seal. McCullough et al. now show that ESCRTs can also promote the scission of membrane tubules with the completely opposite topology. ESCRT-III and IST1 ESCRT subunits form spirals on the outside of membrane tubules and so can mediate the budding of tubules and vesicles into the cytosol. Relatively minor structural rearrangements were required to turn ESCRT function on its head.

Science, this issue p. 1548


The endosomal sorting complexes required for transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure, and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 angstrom resolution cryogenic electron microscopy reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, charged multivesicular body protein 1B (CHMP1B) and increased sodium tolerance 1 (IST1). The inner strand comprises “open” CHMP1B subunits that interlock in an elaborate domain-swapped architecture and is encircled by an outer strand of “closed” IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.

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