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Annu Rev Cell Dev Biol. 2018 Oct 6;34:85-109. doi: 10.1146/annurev-cellbio-100616-060600. Epub 2018 Aug 10.

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes.

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Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA; email:
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
Chan Zuckerberg Biohub, San Francisco, California 94158, USA.


The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.


AAA ATPase; ESCRT pathway; ESCRT-III; Vps4; membrane fission; membrane remodeling

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