The full-length cell-cell fusogen EFF-1 is monomeric and upright on the membrane.
The full-length cell-cell fusogen EFF-1 is monomeric and upright on the membrane.
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DOI：
10.1038/ncomms4912
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发表时间：
2014-05-28
影响因子：
16.6
通讯作者：
Gruenewald, Kay
中科院分区：
文献类型：
--
作者：
Zeev-Ben-Mordehai, Tzviya;Vasishtan, Daven;Siebert, C. Alistair;Gruenewald, Kay
融合剂是重塑脂质双层以促进膜合并的膜蛋白。尽管已经解决了几种融合剂胞外域结构，但有关全长、天然膜锚定的融合剂的结构信息却很少。在这里，我们展示了自然锚定在细胞源性膜囊泡中的秀丽隐杆线虫上皮融合失败 1 (EFF-1) 蛋白的电子冷冻显微镜三维重建。这揭示了膜突出的、不对称的、细长的单体。与病毒II类融合蛋白同源的EFF-1晶体结构的原聚体的灵活拟合表明EFF-1在融合前具有发夹单体构象。这些结构见解与我们对囊泡之间膜融合中间体的观察相结合，使我们能够提出 EFF-1 介导的融合模型。这一过程涉及两个膜上相同的蛋白质进行融合，遵循一种机制，该机制共享 SNARE 介导的融合特征，同时使用单方面作用的 II 类病毒融合蛋白的结构构件。 秀丽隐杆线虫中的细胞与细胞融合是由 EFF-1 和 AFF-1 蛋白介导的。在这里，作者展示了膜中 EFF-1 的电子冷冻显微镜 3D 重建，并将体外膜融合的快照与最近报道的晶体结构相结合，提出了融合过程的机制。
Fusogens are membrane proteins that remodel lipid bilayers to facilitate membrane merging. Although several fusogen ectodomain structures have been solved, structural information on full-length, natively membrane-anchored fusogens is scarce. Here we present the electron cryo microscopy three-dimensional reconstruction of the Caenorhabditis elegans epithelial fusion failure 1 (EFF-1) protein natively anchored in cell-derived membrane vesicles. This reveals a membrane protruding, asymmetric, elongated monomer. Flexible fitting of a protomer of the EFF-1 crystal structure, which is homologous to viral class-II fusion proteins, shows that EFF-1 has a hairpin monomeric conformation before fusion. These structural insights, when combined with our observations of membrane-merging intermediates between vesicles, enable us to propose a model for EFF-1 mediated fusion. This process, involving identical proteins on both membranes to be fused, follows a mechanism that shares features of SNARE-mediated fusion while using the structural building blocks of the unilaterally acting class-II viral fusion proteins. Cell–cell fusion in Caenorhabditis elegans is mediated by EFF-1 and AFF-1 proteins. Here, the authors present an electron cryomicroscopy 3D reconstruction of EFF-1 in the membrane, and combine snapshots of membrane fusion in vitro with a recently reported crystal structure to propose a mechanism for the fusion process.
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影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
7
作者：
Ishihama, Y;Oda, Y;Mann, M
通讯作者：
Mann, M
影响因子：
64.5
作者：
Perez-Vargas, Jimena;Krey, Thomas;Rey, Felix A.
通讯作者：
Rey, Felix A.
DOI：
10.1126/science.1189095
发表时间：
2010-06-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Oren-Suissa M;Hall DH;Treinin M;Shemer G;Podbilewicz B
通讯作者：
Podbilewicz B
影响因子：
7.5
作者：
Graham TR;Kozlov MM
通讯作者：
Kozlov MM