Cell fusion is fundamental for reproduction and organ formation. Fusion between most Caenorhabditis elegans epithelial cells is mediated by the EFF1 fusogen. AFF was first identified in EFF1 mutants. Cell fusion in all epidermal and vulval epithelia was blocked in EFF1 mutants. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeded normally []. AFF1 was established as necessary for this and for the fusion of heterologous cells in C. elegans [].The transmembrane forms of FF proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of FF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity []. C. elegans AFF1 and EFF1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle [].
Cell fusion is fundamental for reproduction and organ formation. Fusion between most Caenorhabditis elegans epithelial cells is mediated by the EFF1 fusogen. AFF was first identified in EFF1 mutants. Cell fusion in all epidermal and vulval epithelia was blocked in EFF1 mutants. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeded normally []. AFF1 was established as necessary for this and for the fusion of heterologous cells in C. elegans [].The transmembrane forms of FF proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of FF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity []. C. elegans AFF1 and EFF1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle [].Cell-cell fusogen EFF/AFF is a three domain protein involved in cell fusion, a process that is essential for development. These proteins can be found either as a monomer or trimer. Crystal structures of the trimer show unambiguous structural homology to class II viral fusion proteins in their characteristic post-fusion hairpin conformation. The trimer subunits feature the three class II beta sandwich domains, termed I, II, and III, organised in the same way as in the viral proteins [].This superfamily represents the domain 3 of the cell-cell fusogen EFF/AFF protein.
