Structural insights into tetraspanin CD9 function
Structural insights into tetraspanin CD9 function
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DOI：
10.1038/s41467-020-15459-7
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发表时间：
2020-03-30
影响因子：
16.6
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Umeda, Rie;Satouh, Yuhkoh;Nureki, Osamu
四跨膜蛋白在从细胞粘附到病毒感染的各种生理过程中发挥关键作用。四跨膜蛋白家族的成员具有四个跨膜结构域和短而大的细胞外环，并与广泛的其他功能蛋白质结合以发挥细胞功能。在这里，我们报告的晶体结构的CD 9和低温电子显微镜结构的CD 9复合物与其单一的跨膜伴侣蛋白，EWI-2。CD 9的倒锥形分子形状在结晶脂质层中产生膜曲率，这解释了CD 9在具有高膜曲率的区域中的定位及其在膜重塑中的意义。CD 9和EWI-2之间的分子相互作用主要通过跨膜区的小残基和蛋白/脂质相互作用介导，而受精试验揭示了LEL区在精卵融合中的关键参与，表明每个结合结构域对其他伴侣蛋白的不同依赖性。
Tetraspanins play critical roles in various physiological processes, ranging from cell adhesion to virus infection. The members of the tetraspanin family have four membrane-spanning domains and short and large extracellular loops, and associate with a broad range of other functional proteins to exert cellular functions. Here we report the crystal structure of CD9 and the cryo-electron microscopic structure of CD9 in complex with its single membrane-spanning partner protein, EWI-2. The reversed cone-like molecular shape of CD9 generates membrane curvature in the crystalline lipid layers, which explains the CD9 localization in regions with high membrane curvature and its implications in membrane remodeling. The molecular interaction between CD9 and EWI-2 is mainly mediated through the small residues in the transmembrane region and protein/lipid interactions, whereas the fertilization assay revealed the critical involvement of the LEL region in the sperm-egg fusion, indicating the different dependency of each binding domain for other partner proteins.