Archaeal roots of eukaryotic class II membrane fusion proteins – ArcFus

Class II membrane fusion proteins have been identified in diverse enveloped viruses (e.g., Zika, chikungunya) as well as in organisms belonging to four of the five eukaryotic kingdoms, where they perform gamete fusion during fertilization. Our bioinformatics analyses suggest an ancestral origin of these proteins in the Archaea, where they seem to be involved in the intercellular spread of mobile genetic elements and present patterns compatible with the folding of class II fusogens. This project aims to 1) perform systematic identification of class II fusogens across the domain Archaea; 2) study their function in vivo; 3) determine the X-ray or cryo-EM structure of the entire ectodomain and its mechanism of action. For this, we will combine approaches from structural biology, genetics, biochemistry and bioinformatics. The expected results will shed new light on the evolution of this widespread family of fusion proteins.