@article{ff9b0dd5c46141928a72e32873b766ab,
title = "The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein",
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.",
keywords = "Chlamydomonas reinhardtii, HAP2, class II fusion protein, crystal structure, gamete fusion, lipid insertion, membrane fusion, sexual reproduction, transmission-blocking malaria vaccine, virus entry",
author = "Juliette F{\'e}dry and Yanjie Liu and G{\'e}rard P{\'e}hau-Arnaudet and Jimin Pei and Wenhao Li and Tortorici, {M. Alejandra} and Fran{\c c}ois Traincard and Annalisa Meola and G{\'e}rard Bricogne and Grishin, {Nick V.} and Snell, {William J.} and Rey, {F{\'e}lix A.} and Thomas Krey",
note = "Funding Information: We thank Francis-Andr{\'e} Wollmann and Sandrine Bujaldon for discussions and help with initial experiments; Fredrick Grinnell, Saikat Mukhopadhyay, Michael Henne, and Margaret Phillips of UT Southwestern for helpful discussions; the crystallization platform of the Pasteur Proteopole for technical help; Remi Fronzes for help with native PAGE experiments; Vincent Olieric and the staff of synchrotron beamlines PX-III at the Swiss Light Source, Proxima-1 and -2 at SOLEIL and ID29 and ID30-3 at the European Synchrotron Radiation Facility for help during data collection; members of the Rey and Snell labs for discussions; and M. Nilges and the Equipement d'excellence CACSICE for providing the Falcon II direct electron detector. F.A.R. acknowledges funding from the ERC Advanced grant project (340371) CelCelFus for this work, which also used general support from Institut Pasteur and CNRS. W.J.S. was supported by a grant from the NIH (GM56778) and acknowledges funding from the UTSW HI/HR Program. N.V.G. is funded, in part, by a grant from the NIH (GM094575) and the Welch Foundation (I-1505). J.F. benefitted from an Allocation minist{\'e}rielle pour l'Ecole Polytechnique AMX. Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
month = feb,
day = "23",
doi = "10.1016/j.cell.2017.01.024",
language = "English (US)",
volume = "168",
pages = "904--915.e10",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}