Origins of the Eukaryotic Endomembrane System: did Arf Family GTPase Function Arise in Archaea? – ArchaeArf

This proposal addresses the origins and deep cellular evolution of the Arf family (Arf_F) of small G proteins (GTPases), providing new insights into eukaryogenesis, with important implications for understanding eukaryotic cellular organization. The eukaryotic Arf proteins (Arf_E, comprised of the Arf, Arl and Sar proteins) are crucial regulators of the structure and function of the endomembrane system, a hallmark of eukaryotic cells. In an exciting recent development, Arf-related proteins have been identified in newly discovered archaea lineages (the Asgard archaea), suggesting that these proteins were present in the common ancestor of archaea and eukaryotes. We will combine bioinformatic, cell biological, biochemical and structural biology approaches to test the hypothesis that these predicted proteins possess the hallmark biochemical features of Arf_E GTPases that enable their function. Small GTPases related to Arfs are among a very few membrane trafficking components present in the Asgard archaea, suggesting that they are one of the key families of proteins that were involved in eukaryogenesis.