The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein

Juliette Fédry, Yanjie Liu, Gérard Péhau-Arnaudet, Jimin Pei, Wenhao Li, M. Alejandra Tortorici, François Traincard, Annalisa Meola, Gérard Bricogne, Nick V. Grishin, William J. Snell, Félix A. Rey, Thomas Krey

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56 Scopus citations

Abstract

Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa—animals, plants, and protists (including important human pathogens like Plasmodium)—suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life.

Original languageEnglish (US)
Pages (from-to)904-915.e10
JournalCell
Volume168
Issue number5
DOIs
StatePublished - Feb 23 2017

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Keywords

  • Chlamydomonas reinhardtii
  • HAP2
  • class II fusion protein
  • crystal structure
  • gamete fusion
  • lipid insertion
  • membrane fusion
  • sexual reproduction
  • transmission-blocking malaria vaccine
  • virus entry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fédry, J., Liu, Y., Péhau-Arnaudet, G., Pei, J., Li, W., Tortorici, M. A., Traincard, F., Meola, A., Bricogne, G., Grishin, N. V., Snell, W. J., Rey, F. A., & Krey, T. (2017). The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. Cell, 168(5), 904-915.e10. https://doi.org/10.1016/j.cell.2017.01.024