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Article Dans Une Revue Current Biology - CB Année : 2017

Structure-function studies link class II viral fusogens with the ancestral gamete fusion protein HAP2

Résumé

The conserved transmembrane protein, HAP2/ GCS1, has been linked to fertility in a wide range of taxa and is hypothesized to be an ancient gamete fusogen. Using template-based structural homology modeling, we now show that the ectodomain of HAP2 orthologs from Tetrahymena thermophila and other species adopt a protein fold remarkably similar to the dengue virus E glycoprotein and related class II viral fusogens. To test the functional significance of this predicted structure, we developed a flow-cytometry-based assay that measures cytosolic exchange across the conjugation junction to rapidly probe the effects of HAP2 mutations in the Tetrahymena system. Using this assay, alterations to a region in and around a predicted "fusion loop" in T. thermophila HAP2 were found to abrogate membrane pore formation in mating cells. Consistent with this, a synthetic peptide corresponding to the HAP2 fusion loop was found to interact directly with model membranes in a variety of biophysical assays. These results raise interesting questions regarding the evolutionary relationships of class II membrane fusogens and harken back to a long-held argument that eukaryotic sex arose as the byproduct of selection for the horizontal transfer of a "selfish" genetic element from cell to cell via membrane fusion.

Dates et versions

hal-02627592 , version 1 (26-05-2020)

Identifiants

Citer

Jennifer Fricke Pinello, Alex L. Lai, Jean K. Millet, Donna Cassidy-Hanley, Jack H. Freed, et al.. Structure-function studies link class II viral fusogens with the ancestral gamete fusion protein HAP2. Current Biology - CB, 2017, 27 (5), pp.651-660. ⟨10.1016/j.cub.2017.01.049⟩. ⟨hal-02627592⟩

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