National Natural Science Foundation of China (NSFC)
中国
Chinese Academy of Sciences
中国
引用
ジャーナル: Cell Rep / 年: 2025 タイトル: Structural basis for the recognition of two different types of receptors by Western equine encephalitis virus. 著者: Bingting Ma / Ziyi Cao / Weijia Ding / Xinzheng Zhang / Ye Xiang / Duanfang Cao / 要旨: Western equine encephalitis virus (WEEV) enters cells via various receptors. Here, we report the cryoelectron microscopy (cryo-EM) structures of WEEV in complex with its receptors PCDH10 and very-low- ...Western equine encephalitis virus (WEEV) enters cells via various receptors. Here, we report the cryoelectron microscopy (cryo-EM) structures of WEEV in complex with its receptors PCDH10 and very-low-density lipoprotein receptor (VLDLR). Structural analysis shows that PCDH10 binds in the cleft formed by adjacent E2-E1 heterodimers of WEEV through its EC1 ectodomain. Residues of viral envelope proteins involved in the interactions with PCDH10 EC1 are unique to WEEV. The strain-specific receptor VLDLR binds WEEV strain McMillan through two consecutive ecto-LDLR class A (LA) repeats. LA1-2, LA2-3, LA3-4, LA4-5, and LA5-6 of VLDLR all have detectable interactions with WEEV. Detailed structures of WEEV in complex with LA1-2 and LA2-3 show that the N-terminal LA repeat binds in the cleft and that the C-terminal LA repeat is attached to the E2 B domain. The acquisition of a single E2 mutation (V265F) allows WEEV strain 71V-1658, originally unable to bind VLDLR, to gain this receptor-binding ability. The binding of VLDLR to WEEV is in a mode different from those of other alphaviruses.