The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.
The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.
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DOI：
10.1016/j.cell.2017.01.024
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发表时间：
2017-02-23
期刊：
影响因子：
64.5
通讯作者：
Krey T
中科院分区：
文献类型：
--
作者：
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
有性生殖在真核生物中几乎是普遍的，并且涉及雄性和雌性单倍体配子融合成二倍体细胞。据推测，精子限制性单程跨膜蛋白HAP 2-GCS 1在膜合并中发挥作用。它存在于主要的真核生物类群-动物，植物和原生生物（包括重要的人类病原体，如疟原虫）-表明许多真核生物共享一个共同的配子融合机制。在这里，我们报告相结合的生物信息学，生物化学，突变和X射线晶体学研究的单细胞衣藻莱茵衣藻HAP 2，揭示同源性II类病毒膜融合蛋白。我们进一步表明，通过诱变或通过抗体靶向对应于融合环的片段阻断配子融合。这些结果表明，HAP 2是配子融合剂，并提出了类似于病毒融合的作用机制，表明了一种阻断疟原虫传播的方法，并强调了病毒-细胞遗传交换对真核生物进化的影响。原始配子融合原HAP 2与II类病毒融合蛋白具有同源性，HAP 2通过疏水融合环插入靶配子膜，HAP 2连接病毒进入靶细胞和有性生殖的起源，HAP 2是用于阻断多界受精的性别特异性靶标。
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. The primordial gamete fusogen HAP2 exhibits homology to class II viral fusion proteins HAP2 inserts into the target gamete membrane via a hydrophobic fusion loop HAP2 links virus entry into target cells and the origins of sexual reproduction HAP2 is a sex-specific target for blocking fertilization in multiple kingdoms Gamete fusion across eukaryotic branches uses an ancient factor homologous to viral fusion proteins.