美国华盛顿大学医学院Michael S. Diamond研究团队，揭示了东部马脑炎病毒(EEEV)使用极低密度脂蛋白受体(VLDLR)的结构和功能基础。相关论文发表在2024年1月3日出版的《细胞》杂志上。
通过解析EEEV- VLDLR复合物的多个低温电镜结构并进行诱变和功能研究，他们发现EEEV使用多个位点(E1/E2间隙和E2 A结构域)同时参与多个LDLR A型(LA)结构域。然而，没有一个单一的LA结构域是必要的或足以支持有效的EEEV感染。
虽然所有EEEV菌株都具有两个VLDLR结合位点的保守性，但EEEV PE-6菌株和其他一些EEE复合物成员具有单个氨基酸取代，可以将LA结构域结合到E2 B结构域的其他位点上。这些结构和功能分析为最小的VLDLR诱饵受体的设计提供了信息，该受体可以中和EEEV感染并保护小鼠免受致命攻击。
据悉，VLDLR由8个LA结构域组成，支持远亲甲病毒的进入，包括EEEV和塞姆利基森林病毒(SFV)。
附：英文原文
Title: Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus
Author: Lucas J. Adams, Saravanan Raju, Hongming Ma, Theron Gilliland, Douglas S. Reed, William B. Klimstra, Daved H. Fremont, Michael S. Diamond
Issue&Volume: 2024-01-03
Abstract: The very-low-density lipoprotein receptor (VLDLR) comprises eight LDLR type A (LA)domains and supports entry of distantly related alphaviruses, including Eastern equineencephalitis virus (EEEV) and Semliki Forest virus (SFV). Here, by resolving multiplecryo-electron microscopy structures of EEEV-VLDLR complexes and performing mutagenesisand functional studies, we show that EEEV uses multiple sites (E1/E2 cleft and E2A domain) to engage more than one LA domain simultaneously. However, no single LAdomain is necessary or sufficient to support efficient EEEV infection. Whereas allEEEV strains show conservation of two VLDLR-binding sites, the EEEV PE-6 strain anda few other EEE complex members feature a single amino acid substitution that enablesbinding of LA domains to an additional site on the E2 B domain. These structural andfunctional analyses informed the design of a minimal VLDLR decoy receptor that neutralizesEEEV infection and protects mice from lethal challenge.
DOI: 10.1016/j.cell.2023.11.031
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01318-1
来源：科学网 小柯机器人