CONICET | Buscador de Institutos y Recursos Humanos

The Fusexin superfamily was recently established when 3distinct families of membrane fusion proteins were shown to share the samefold. Thus Hap2 -eukaryotic gamete fusogens-, EFF-1/AFF-1 -somatic cell-cellfusion proteins implicated in tissue development of nema-todes-and Class IIviral fusogens -which fuse enveloped viruses to their target cells-, havecommon ancestry and similar action mecha-nisms.This shared ancestry across theeukaryotic domain of life and the virosphere points to an intriguingevolutionary history that lead us be as exhaustive as possible in searching formorepossible homologues. Using metagenomic data and a thorough search strategy,based on highly sensitive similarity/homology search tools (Psi-BLAST, HMMERand HHpred) coupled with structural prediction algorithms, we were able toidentify new fusexin candidate proteins. Topology and structural modeling ofthe fusexin candidates indicate that this superfamily, although conserved inthe extracellular domain, shows a wide array of membrane anchors and potentialdisulfide bonds. Since these candidates belong totaxonomic lineages wherefusexins were assumed to be absent, our findings give a novel picture of thethe early evolutionary history of this superfamily. Thesenewfound fusexincandidatesmay lead to a deeper understanding of the early stages of sexualreproduction.The candidates are currently being tested in different cellculture systems to study whether they are bona fide fusogens and to deter-minetheir mechanisms of action.

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