Structural basis for receptor recognition by Lujo virus
Structural basis for receptor recognition by Lujo virus
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DOI：
10.1038/s41564-018-0224-5
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发表时间：
2018-10-01
影响因子：
28.3
通讯作者：
Diskin, Ron
中科院分区：
文献类型：
--
作者：
Cohen-Dvashi, Hadas;Kilimnik, Itay;Diskin, Ron
卢霍病毒（LUJV）已成为一种高度致命的人类病原体。尽管它属于沙粒病毒科，但LUJV不属于已知的该病毒家族的旧和新世界组。同样，最近发现LUJV使用neuropilin-2 （NRP2）作为细胞受体，而不是旧大陆和新世界沙粒病毒使用的典型受体。一种致命的病原体以前所未有的途径进入人类群体，这引发了许多关于细胞识别机制的问题。为了提供对抗LUJV的基础，并增加我们对沙粒病毒新受体进化过程中分子变化的总体理解，我们使用x射线晶体学揭示了LUJV的GP1受体结合域（LUJV(GP1)）如何识别NRP2。结构数据显示，LUJV（GP1）与旧大陆沙粒病毒比与新大陆沙粒病毒更相似。实验验证的结构分析进一步表明，NRP2识别依赖于金属离子，完整的NRP2结合位点是在三聚体尖刺的背景下形成的。综上所述，我们的数据提供了LUJV细胞附着步骤的机制，并为对抗该病原体提供了不可或缺的信息。
Lujo virus (LUJV) has emerged as a highly fatal human pathogen. Despite its membership among the Arenaviridae, LUJV does not classify with the known Old and New World groups of that viral family. Likewise, LUJV was recently found to use neuropilin-2 (NRP2) as a cellular receptor instead of the canonical receptors used by Old World and New World arenaviruses. The emergence of a deadly pathogen into human populations using an unprecedented entry route raises many questions regarding the mechanism of cell recognition. To provide the basis for combating LUJV in particular, and to increase our general understanding of the molecular changes that accompany an evolutionary switch to a new receptor for arenaviruses, we used X-ray crystallography to reveal how the GP1 receptor-binding domain of LUJV (LUJV(GP1)) recognizes NRP2. Structural data show that LUJV(GP1) is more similar to Old World than to New World arenaviruses. Structural analysis supported by experimental validation further suggests that NRP2 recognition is metal-ion dependent and that the complete NRP2 binding site is formed in the context of the trimeric spike. Taken together, our data provide the mechanism for the cell attachment step of LUJV and present indispensable information for combating this phatogen.