THE GODS OF THE ACTIN CYTOSKELETON

Asgard archaea are named after the gods of Norse mythology, including Heimdall, Loki, Odin, Thor, Hel and Gerd. Metagenomics sequencing has revealed that Asgard archaea contain potential homologs to eukaryotic genes. Several of these gene products are involved in forming the cytoskeleton and modifying membranes, hallmarks of eukaryotic cells. Thus, the hypothesis that the source eukaryotic cell arose from the Archaea domain now has potential model organisms to study that may have the pre-eukaryotic properties. However, only one Asgard archaea has been successfully imaged and cultivated, bringing in to question whether these archaea generally exhibit eukaryotic characteristics. Recently, we published evidence that the Asgard versions of the actin and its regulators, profilins and gelsolins, are functional at the protein level. In eukaryotes, force from directed actin polymerization drives membrane remodelling through filament nucleation and elongation machineries such as formins, which recruit the profilin/actin complex to initiate polymerization. Many of these interactions are regulated by the phospholipid PIP2. We demonstrated that LokiProfilin is a true profilin being functional in regulating mammalian actin in vitro. We determined the LokiProfilin/mammalian actin crystal structure, which verified the conserved actin interaction (above). Asgard profilins appear to be primitive actin regulators since they do not interact with formin polyproline sequences but do interact with phospholipids, features of eukaryotic profilins. Through structural and biochemical studies we have discovered that some thorarchaeota gelsolins (2DGel) are able sever actin filaments in a calcium-dependent manner, whilst single domain ProGels are more similar to cofilin, in their binding to actin.  Hence, we have generated the first experimental data at the protein level that suggests that eukaryotes may have evolved from the Archaea domain. Here, we will build on these initial findings to study other eukaryotic-like proteins encoded from the Asgard genomes.