Evolutionary diversification of the HAP2 membrane insertion motifs to drive gamete fusion across eukaryotes
Evolutionary diversification of the HAP2 membrane insertion motifs to drive gamete fusion across eukaryotes
复制标题
DOI：
10.1371/journal.pbio.2006357
复制
发表时间：
2018-08-01
期刊：
影响因子：
9.8
通讯作者：
Krey, Thomas
中科院分区：
文献类型：
--
作者：
Fedry, Juliette;Forcina, Jennifer;Krey, Thomas
HAPLESS 2（HAP 2）是一种广泛保守的配子表达的跨膜蛋白，其最近被证明与病毒II类融合蛋白结构同源，所述病毒II类融合蛋白通过将融合环插入宿主膜中来启动与宿主细胞的融合。然而，HAP 2融合环的功能构象仍然未知，因为报道的莱茵衣藻HAP 2的X射线结构缺乏这个关键区域。在这里，我们报告了一个结构引导的对齐，揭示了多样化的建议HAP 2融合环。代表性的晶体结构显示，在开花植物中，HAP 2具有单个突出的融合环，在其顶端投射两亲性螺旋，而在锥虫中，HAP 2的三个小的非极性环准备与靶膜相互作用。拟南芥HAP 2两亲性融合螺旋的详细结构-功能分析定义了膜插入和配子融合所必需的关键残基。我们的研究表明，HAP 2可能已经进化出多种膜插入模式，以适应它在真核生物进化过程中遇到的膜环境的多样性。
HAPLESS2 (HAP2) is a broadly conserved, gamete-expressed transmembrane protein that was shown recently to be structurally homologous to viral class II fusion proteins, which initiate fusion with host cells via insertion of fusion loops into the host membrane. However, the functional conformation of the HAP2 fusion loops has remained unknown, as the reported X-ray structure of Chlamydomonas reinhardtii HAP2 lacked this critical region. Here, we report a structure-guided alignment that reveals diversification of the proposed HAP2 fusion loops. Representative crystal structures show that in flowering plants, HAP2 has a single prominent fusion loop projecting an amphipathic helix at its apex, while in trypanosomes, three small nonpolar loops of HAP2 are poised to interact with the target membrane. A detailed structure-function analysis of the Arabidopsis HAP2 amphipathic fusion helix defines key residues that are essential for membrane insertion and for gamete fusion. Our study suggests that HAP2 may have evolved multiple modes of membrane insertion to accommodate the diversity of membrane environments it has encountered during eukaryotic evolution.