Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
J Mol Biol. 2019 May 17;431(11):2095-2111. doi: 10.1016/j.jmb.2019.04.012. Epub 2019 Apr 18.
Lassa virus (LASV) is a notorious human pathogen in West Africa. Its class I trimeric spike complex displays a distinct architecture, and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2) in its post-fusion conformation. GP2 adopts a canonical helical bundle configuration similarly to other viruses in its family. The core packing of GP2, however, is more organized compared to GP2 from other viruses reducing the formation of internal hydrophobic cavities. We demonstrate a link between the formation of such unfavorable hydrophobic cavities and the efficiencies of membrane fusion and cell entry. Our study suggests that LASV has evolved a more efficient membrane fusogen compared to other viruses from its family by optimizing the post-fusion configuration of its GP2 module.
拉沙病毒（LASV）是西非一种臭名昭著的人类病原体。其 I 类三聚体刺突复合物呈现出独特的结构，其细胞进入机制涉及到其他相关病毒所没有的独特属性。我们确定了 LASV 刺突复合物中 GP2 融合糖蛋白的晶体结构（GP2）处于融合后构象。GP2 采用与家族中其他病毒类似的典型螺旋束构象。然而，与其他病毒的 GP2 相比，GP2 的核心包装更加有序，减少了内部疏水性腔的形成。我们证明了形成这种不利的疏水性腔与膜融合和细胞进入效率之间存在联系。我们的研究表明，与家族中的其他病毒相比，LASV 通过优化其 GP2 模块的融合后构象，进化出了一种更有效的膜融合剂。
