Abstract
Self-assembly of ESCRT-III complex is a critical step in all ESCRT-dependent events. ESCRT-III hetero-polymers adopt variable architectures, but the mechanisms of inter-subunit recognition in these hetero-polymers to create flexible architectures remain unclear. We demonstrate in vivo and in vitro that the Saccharomyces cerevisiae ESCRT-III subunit Snf7 uses a conserved acidic helix to recruit its partner Vps24. Charge-inversion mutations in this helix inhibit Snf7-Vps24 lateral interactions in the polymer, while rebalancing the charges rescues the functional defects. These data suggest that Snf7-Vps24 assembly occurs through electrostatic interactions on one surface, rather than through residue-to-residue specificity. We propose a model in which these cooperative electrostatic interactions in the polymer propagate to allow for specific inter-subunit recognition, while sliding of laterally interacting polymers enable changes in architecture at distinct stages of vesicle biogenesis. Our data suggest a mechanism by which interaction specificity and polymer flexibility can be coupled in membrane-remodeling heteropolymeric assemblies.
Highlights
Eukaryotic organelles that are demarcated by membranes undergo continuous remodeling to maintain their integrity and function
The structure of the organized CHMP1B in its helical assembly with IST1 suggests that the same core interface drives ESCRT-III polymerization with an evolutionarily conserved mechanism of ESCRT-III assembly (McCullough et al, 2015; McCullough et al, 2018; Talledge et al, 2019)
The core components of the ESCRT-III complex are essential for numerous biological reactions
Summary
Eukaryotic organelles that are demarcated by membranes undergo continuous remodeling to maintain their integrity and function. Control the remodeling at different organelles (Zimmerberg and Kozlov, 2006) This polymerization-mediated membrane remodeling in eukaryotes is important for various cellular events such as trafficking, cell-division and migration. Structural homologs of actin and tubulin (that include FtsZ and MreB proteins) form heteropolymers, which deform and remodel membranes, leading to cell shape maintenance and division (Eun et al, 2015). In most cases these proteins are recruited to the membrane from the cytosol as monomers, polymerization occurs on the 2D membrane, which generates the mechanical force to bend membranes. Given the functional importance of polymerization, elucidating mechanisms of how these various machines recognize their partners to form heteropolymers, and how these polymers adapt to physical and mechanical changes in the cellular environment is critical to our overall understanding of how cells control membrane homeostasis
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