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

doi:10.1016/j.cell.2017.01.024

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

^*Corresponding author for this work

Institute of Biochemistry

147 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 language	English
Journal	Cell
Volume	168
Issue number	5
Pages (from-to)	904-915.e10
ISSN	0092-8674
DOIs	https://doi.org/10.1016/j.cell.2017.01.024
Publication status	Published - 23.02.2017

Funding

We thank Francis-Andr? 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?rielle pour l'Ecole Polytechnique AMX.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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.",

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AU - Pei, Jimin

AU - Li, Wenhao

AU - Tortorici, M. Alejandra

AU - Traincard, François

AU - Meola, Annalisa

AU - Bricogne, Gérard

AU - Grishin, Nick V.

AU - Snell, William J.

AU - Rey, Félix A.

AU - Krey, Thomas

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N2 - 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.

AB - 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.

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

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