Abstract
ESCRT-III polymerization is required for all endosomal sorting complex required for transport (ESCRT)-dependent events in the cell. However, the relative contributions of the eight ESCRT-III subunits differ between each process. The minimal features of ESCRT-III proteins necessary for function and the role for the multiple ESCRT-III subunits remain unclear. To identify essential features of ESCRT-III subunits, we previously studied the polymerization mechanisms of two ESCRT-III subunits Snf7 and Vps24, identifying the association of the helix-4 region of Snf7 with the helix-1 region of Vps24 (Banjade et al., 2019a). Here, we find that mutations in the helix-1 region of another ESCRT-III subunit Vps2 can functionally replace Vps24 in Saccharomyces cerevisiae. Engineering and genetic selections revealed the required features of both subunits. Our data allow us to propose three minimal features required for ESCRT-III function - spiral formation, lateral association of the spirals through heteropolymerization, and binding to the AAA + ATPase Vps4 for dynamic remodeling.
Highlights
endosomal sorting complex required for transport (ESCRT) control a growing list of membrane remodeling events in cells (Vietri et al, 2020)
Vps20, Snf7, Vps24, and Vps2 have been studied in greater detail, because they are individually essential for multivesicular body (MVB) biogenesis in yeast, the earliest ascribed role for ESCRTs
Toward a comprehensive understanding of each ESCRT-III subunit, studies in MVB biogenesis have provided important clues regarding their individual roles in membrane remodeling
Summary
ESCRTs (endosomal sorting complexes required for transport) control a growing list of membrane remodeling events in cells (Vietri et al, 2020). Our understanding of the mechanisms of ESCRT-III assembly has increased substantially in the last decade (Henne et al, 2012; Shen et al, 2014; Cashikar et al, 2014; Chiaruttini et al, 2015; McCullough et al, 2015; Tang et al, 2015; Adell et al, 2017; Mierzwa et al, 2017; Schoneberg et al, 2018; Goliand et al, 2018; Maity et al, 2019; Bertin et al, 2020; Moser von Filseck et al, 2020; Nguyen et al, 2020; Pfitzner et al, 2020). Toward a comprehensive understanding of each ESCRT-III subunit, studies in MVB biogenesis have provided important clues regarding their individual roles in membrane remodeling
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