The ESCRT III complex consists of at least 18 proteins and is required for the sorting and concentration of proteins resulting in the entry of these proteins into the invaginating vesicles of the multivesicular body (Babst et al. 2002). The sequential action of ESCRT-0, -I, and -II together with the ordered assembly of ESCRT-III links membrane invagination to cargo sorting. Membrane scission in the neck of the growing vesicle releases mature, cargo-laden vesicles into the lumen (Buchkovich et al. 2013, Adell et al. 2014). ESCRT-III is critical for late steps in MVB sorting, such as membrane invagination and final cargo sorting and recruitment of late-acting components of the sorting machinery (Adell et al. 2014). SNF7 is the most abundant ESCRT-III subunit which forms membrane-sculpting filaments with 30 Å periodicity and a exposed cationic membrane-binding surface (Tang et al. 2015). Its activation requires a prominent conformational rearrangement to expose protein-membrane and protein-protein interfaces. SNF7 filaments then form spirals that may function as spiral springs (Chiaruttini et al. 2015). The elastic expansion of compressed SNF7 spirals generates an area difference between the two sides of the membrane and thus curvature, which could be the origin of membrane deformation leading eventually to fission. SNF7 recruits BRO1, which in turn recruits DOA4, which deubiquitinates cargos before their enclosure within MVB vesicles (Amerik et al. 2000, Kim et al. 2005). ESCRT-III is also recruited to the nuclear envelope (NE) by integral INM proteins to surveil and clear defective nuclear pore complex (NPC) assembly intermediates to ensure the fidelity of NPC assembly (Webster et al. 2014).Vsp4 is an ATPase that provides the force generation and membrane scission by ESCRT-III (Schöneberg et al. 2018). The sorting of transmembrane proteins (e.g., cell surface receptors) into the multivesicular body (MVB) pathway to the lysosomal/vacuolar lumen requires the function of the ESCRT protein complexes. The soluble coiled-coil-containing proteins Vps2, Vps20, Vps24, and Snf7 are recruited from the cytoplasm to endosomal membranes where they oligomerize into a protein complex, ESCRT-III. ESCRT-III contains two functionally distinct subcomplexes. The Vps20-Snf7 subcomplex binds to the endosomal membrane, in part via the myristoyl group of Vps20. The Vps2-Vps24 subcomplex binds to the Vps20-Snf7 complex and thereby serves to recruit additional cofactors to this site of protein sorting. Evidence for a role for ESCRT-III in sorting and/or concentration of MVB cargoes has been forthcoming (Babst et al. 2002). ESCRT-dependent protein sorting is required for the viability of yeast clathrin-mediated endocytosis mutants (Hoban et al. 2020).
ESCRT III of Saccharomyces cerevisiae
SNF7, DID1, VPS32; 240 aas; P39929
VPS2, DID4, CHM2, GRD7, REN1, VPL2; 232 aas; P36108
VPS24, DID3; 224 aas; P36095
VPS20, ASI1, CHM6, VPT20; 221 aas; Q04272
VPS4 ATPase, CSC1, DID6,END13, GRD13, VPL4; 437 aas; P52917 Plus 20 auxiliary constituents.