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

Research output: Contribution to journalArticle

45 Citations (Scopus)

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

Fingerprint

Germ Cells
Fusion reactions
Plasmodium
Proteins
Viral Matrix Proteins
Membrane Fusion Proteins
Viral Fusion Proteins
Chlamydomonas reinhardtii
Virus Internalization
Haploidy
Computational Biology
Diploidy
Mutagenesis
Reproduction
Spermatozoa
Pathogens
Bioinformatics
Algae
Viruses
X-Rays

Keywords

  • Chlamydomonas reinhardtii
  • class II fusion protein
  • crystal structure
  • gamete fusion
  • HAP2
  • 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., ... 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

The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. / Fédry, Juliette; Liu, Yanjie; Péhau-Arnaudet, Gérard; Pei, Jimin; Li, Wenhao; Tortorici, M. Alejandra; Traincard, François; Meola, Annalisa; Bricogne, Gérard; Grishin, Nick V.; Snell, William J.; Rey, Félix A.; Krey, Thomas.

In: Cell, Vol. 168, No. 5, 23.02.2017, p. 904-915.e10.

Research output: Contribution to journalArticle

Fédry, J, Liu, Y, Péhau-Arnaudet, G, Pei, J, Li, W, Tortorici, MA, Traincard, F, Meola, A, Bricogne, G, Grishin, NV, Snell, WJ, Rey, FA & Krey, T 2017, 'The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein', Cell, vol. 168, no. 5, pp. 904-915.e10. https://doi.org/10.1016/j.cell.2017.01.024
Fédry J, Liu Y, Péhau-Arnaudet G, Pei J, Li W, Tortorici MA et al. The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. Cell. 2017 Feb 23;168(5):904-915.e10. https://doi.org/10.1016/j.cell.2017.01.024
Fédry, Juliette ; Liu, Yanjie ; Péhau-Arnaudet, Gérard ; Pei, Jimin ; Li, Wenhao ; Tortorici, M. Alejandra ; Traincard, François ; Meola, Annalisa ; Bricogne, Gérard ; Grishin, Nick V. ; Snell, William J. ; Rey, Félix A. ; Krey, Thomas. / The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein. In: Cell. 2017 ; Vol. 168, No. 5. pp. 904-915.e10.
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