Discovery of archaeal fusexins homologous to eukaryotic HAP2/GCS1 gamete fusion proteins.
Moi, D., Nishio, S., Li, X., Valansi, C., Langleib, M., Brukman, N. G., Flyak, K., Dessimoz, C., de Sanctis, D., Tunyasuvunakool, K., Jumper, J., Grana, M., Romero, H., Aguilar, P. S., Jovine, L. and Podbilewicz, B.
Instituto de Fisiologia, Biologia Molecular y Neurociencias (IFIBYNE-CONICET), Buenos Aires, Argentina.
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Department of Biology, Technion- Israel Institute of Technology, Haifa, Israel.
Unidad de Genomica Evolutiva, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay.
Unidad de Bioinformatica, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Department of Genetics, Evolution and Environment, Centre for Life's Origins and Evolution, University College London, London, UK.
Department of Computer Science, University College London, London, UK.
ESRF-The European Synchrotron, Grenoble, France.
DeepMind, London, UK.
Unidad de Bioinformatica, Institut Pasteur de Montevideo, Montevideo, Uruguay. mgrana@pasteur.edu.uy.
Unidad de Genomica Evolutiva, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay. eletor@fcien.edu.uy.
Centro Universitario Regional Este - CURE, Centro Interdisciplinario de Ciencia de Datos y Aprendizaje Automatico - CICADA, Universidad de la Republica, Montevideo, Uruguay. eletor@fcien.edu.uy.
Instituto de Fisiologia, Biologia Molecular y Neurociencias (IFIBYNE-CONICET), Buenos Aires, Argentina. paguilar@iib.unsam.edu.ar.
Instituto de Investigaciones Biotecnologicas Universidad Nacional de San Martin (IIB-CONICET), San Martin, Buenos Aires, Argentina. paguilar@iib.unsam.edu.ar.
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. luca.jovine@ki.se.
Department of Biology, Technion- Israel Institute of Technology, Haifa, Israel. podbilew@technion.ac.il.
Sexual reproduction consists of genome reduction by meiosis and subsequent gamete fusion. The presence of genes homologous to eukaryotic meiotic genes in archaea and bacteria suggests that DNA repair mechanisms evolved towards meiotic recombination. However, fusogenic proteins resembling those found in gamete fusion in eukaryotes have so far not been found in prokaryotes. Here, we identify archaeal proteins that are homologs of fusexins, a superfamily of fusogens that mediate eukaryotic gamete and somatic cell fusion, as well as virus entry. The crystal structure of a trimeric archaeal fusexin (Fusexin1 or Fsx1) reveals an archetypical fusexin architecture with unique features such as a six-helix bundle and an additional globular domain. Ectopically expressed Fusexin1 can fuse mammalian cells, and this process involves the additional globular domain and a conserved fusion loop. Furthermore, archaeal fusexin genes are found within integrated mobile elements, suggesting potential roles in cell-cell fusion and gene exchange in archaea, as well as different scenarios for the evolutionary history of fusexins.
Nature Communications 13(1): 3880 (2022)