Localization of Asgard archaeal ESCRT proteins to eukaryotic cellular structures

The emergence of internal membrane systems was a defining step in eukaryogenesis, but how pre-eukaryotic proteins were adapted to these novel compartments and structures remains unclear. Asgard archaea, the closest known prokaryotic relatives of eukaryotes, encode homologs of ESCRT (Endosomal Sorting Complex Required for Transport) proteins, which mediate membrane remodeling in eukaryotic cells, processes ranging from endosomal sorting to cytokinetic abscission. Here, we show that ESCRT-II and ESCRT-III homologs, VSP4 and ubiquitin from the Asgard achaeon Promethearchaeum syntrophicum (MK-D1) are recruited to discrete structures when expressed in human cells. These archaeal proteins localize to canonical eukaryotic ESCRT recruitment sites, midbodies and centrosomes, structures which are absent from MK-D1. This localization reflects conserved molecular interactions that predate the emergence of eukaryotic internal membranes and other eukaryotic cellular structures. These findings support a model in which protein machines were repurposed to support cellular complexity during eukaryogenesis, allowing the integration of ancestral ESCRT molecular functions and networks in to novel cellular architectures. • Asgard archaeal (MK-D1) ESCRT structural models reveal conserved eukaryotic cores with divergent regulatory domains. • MK-D1 ubiquitin, ESCRT-II, ESCRT-III, and VPS4 proteins localize with to midbodies in eukaryotic cells. • MK-D1 ubiquitin, ESCRT-II, ESCRT-III, and VPS4 proteins localize with to centrosomes in eukaryotic cells. • The ancestral archaeal ESCRT cell membrane acting system was repurposed during eukaryogenesis to promote and support cellular complexity.