Structural Basis of Eukaryotic Cell-Cell Fusion
Structural Basis of Eukaryotic Cell-Cell Fusion
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DOI：
10.1016/j.cell.2014.02.020
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发表时间：
2014-04-10
期刊：
影响因子：
64.5
通讯作者：
Rey, Felix A.
中科院分区：
文献类型：
--
作者：
Perez-Vargas, Jimena;Krey, Thomas;Rey, Felix A.
细胞-细胞融合蛋白在发育中是必不可少的。在这里，我们表明，C。线虫细胞-细胞融合蛋白EFF-1在结构上与II类病毒融合蛋白同源。EFF-1三聚体的2.6埃晶体结构显示出与融合后II类病毒融合蛋白相同的3D折叠和四级构象，尽管它缺乏非极性“融合环”，表明它不插入靶膜。EFF-1以前被证明是需要在两个细胞融合，我们表明，阻断EFF-1三聚体阻断融合反应。总之，这些数据表明，尽管由病毒蛋白驱动的膜融合需要利用非极性环，但EFF-1驱动的细胞融合需要反式三聚化，使得锚定在两个相对膜中的跨膜区段在EFF-1三聚体的尖端接触，然后类似于SNARE介导的囊泡融合，将两个膜合二为一。
Cell-cell fusion proteins are essential in development. Here we show that the C. elegans cell-cell fusion protein EFF-1 is structurally homologous to viral class II fusion proteins. The 2.6 angstrom crystal structure of the EFF-1 trimer displays the same 3D fold and quaternary conformation of postfusion class II viral fusion proteins, although it lacks a nonpolar "fusion loop," indicating that it does not insert into the target membrane. EFF-1 was previously shown to be required in both cells for fusion, and we show that blocking EFF-1 trimerization blocks the fusion reaction. Together, these data suggest that whereas membrane fusion driven by viral proteins entails leveraging of a nonpolar loop, EFF-1-driven fusion of cells entails trans-trimerization such that transmembrane segments anchored in the two opposing membranes are brought into contact at the tip of the EFF-1 trimer to then, analogous to SNARE-mediated vesicle fusion, zip the two membranes into one.