Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Buenos Aires, Argentina.
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Nat Commun. 2022 Jul 6;13(1):3880. doi: 10.1038/s41467-022-31564-1.
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.
有性生殖包括通过减数分裂减少基因组和随后的配子融合。古菌和细菌中存在与真核减数分裂基因同源的基因表明，DNA 修复机制朝着减数分裂重组进化。然而，迄今为止，在原核生物中尚未发现类似于真核生物配子融合中发现的融合蛋白。在这里，我们鉴定出与 fusexin 同源的古菌蛋白，fusexin 是一个介导真核配子和体细胞融合以及病毒进入的融合蛋白超家族。一个三聚体古菌 fusexin（Fusexin1 或 Fsx1）的晶体结构揭示了一个典型的 fusexin 结构，具有独特的特征，如六螺旋束和一个额外的球状结构域。异位表达的 Fusexin1 可以融合哺乳动物细胞，这个过程涉及到额外的球状结构域和一个保守的融合环。此外，古菌 fusexin 基因存在于整合的移动元件中，这表明它们在古菌中的细胞-细胞融合和基因交换中具有潜在的作用，以及 fusexin 的不同进化历史场景。
