Structure and Fonction of ESCRT-III complexe
The endosomal sorting complex required for transport (ESCRT) machinery catalyzes many divergent membrane remodeling processes including the formation of multivesicular endosomes, cytokinesis, nuclear envelope reformation, membrane repair, exosome biogenesis, enveloped virus budding and many other processes.
Common to all ESCRT-catalyzed processes in eukaryotes, archaea and bacteria is the recruitment of ESCRT-III proteins that polymerize to generate and/or to stabilize membranes with either flat, negatively or positively curved geometries. The principal function of the polymers is to induce membrane constriction via outside-in fission of tubular structures with ESCRT-III protein coats on the outside of a membrane tube or inside-out fission with ESCRT-III polymers assembled within membrane neck/tube structures formed during vesicle and virus budding or at the cytokinetic midbody.
Humans express eight ESCRT-III proteins (named CHMP) that can comprise several isoforms per member. ESCRT-III composed of CHMP4, CHMP2 and CHMP3 constitute a minimal machinery that together with VPS4 catalyzes membrane fission from within membrane necks and catalizes the HIV budding.
ESCRT-III CHMP2A and CHMP3 combine to form filaments that organize themselves into helical tubular structures with defined diameters in vitro, which have been suggested to stabilize negative membrane curvature. These polymers recruit VPS4 which constricts these filaments producing dome-like end caps prior to complete polymer disassembly in vitro in agreement with permanent ESCRT-III turn-over in vivo. Because most ESCRT-catalyzed processes act on negatively curved membranes to catalyze inside-out membrane fission, we set out to determine the structural basis of ESCRT-III stabilizing negatively curved membranes. We reconstituted CHMP2A-CHMP3 polymers within membrane tubes and solved their structure by cryo electron microscopy.