A eukaryotic-like phospholipid transfer protein conserved in Asgard archaea

Eukaryotic cells rely on conserved lipid transfer proteins (LTPs) to shuttle insoluble phospholipids between membranes and support organelle proliferation. Because cells lacking organelles do not require extensive lipid transport networks, it is not known if such machinery had to evolve during eukaryogenesis. Here we describe a class of phospholipid transporters in Asgard archaea that share structural and functional features with eukaryotic LTPs of the START domain superfamily. Asgard genomes encode three START protein classes, StarAsg1-3, conserved across most phyla, of which only StarAsg1 has the large hydrophobic cavity and membrane-docking motifs required for lipid transfer. StarAsg1 from Lokiarchaeia binds anionic membranes in vitro and in yeast, extracts phospholipids, and transfers several phospholipid classes between membranes, as eukaryotic START LTPs do. Phylogeny suggests eukaryotic LTPs could share ancestry with StarAsg1, while StarAsg2/3 group with a eukaryotic Hsp90 co-chaperone. Inter-membrane lipid transport may have predated eukaryogenesis and subsequently facilitated organelle proliferation.