Molecular basis for cellular compartmentalization by an ancient membrane fission mechanism
Espadas, J.; Souza, D. P.; Hakala, M.; Garcia-Arcos, J. M.; Tran, J.; Kumar, A.; Marcuello, C.; Merino, A.; Colom, A.; Vanni, S.; Kaksonen, M.; Baum, B.; Toret, C. P.; Roux, A.
Show abstract
The emergence of cell compartmentalization depends on membrane fission to create the endomembrane compartments. In eukaryotes, membrane fission is commonly executed by ESCRT-III, a protein complex conserved in all domains of life. However, whether membrane fission was an ancestral ESCRT-III activity predating eukaryogenesis remains unknown. Here we show that ESCRT-IIIA from Asgard Heimdallarchaeota, the closest archaeal relatives of eukaryotes, performs membrane fission through an N-terminal amphipathic helix, which we term Hofund. In eukaryotes, Hofund is fragmented across ESCRT-IIIA paralogs, and disrupting these regions causes severe fission defect in yeast. Remarkably, Heimdallarchaeota Hofund restores fission when fused to defective eukaryotic paralogs. These findings suggest that ESCRT-III-mediated fission arose before eukaryogenesis and later diversified to support the regulatory complexity of eukaryotic compartmentalization.
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