9L1N

Structure of Western equine encephalitis virus 71V1658 strain VLP in complex with human PCDH10 EC1

Summary for 9L1N

• Entry DOI: 10.2210/pdb9l1n/pdb
• EMDB information: 62749
• Descriptor: E1 glycoprotein, E2 glycoprotein, Capsid glycoprotein, ... (5 entities in total)
• Functional Keywords: western equine encephalitis virus, weev, pcdh10, ec1, receptor, complex, glycoprotein, viral protein
• Biological source: Western equine encephalitis virus (WEEV); More
• Total number of polymer chains: 13
• Total formula weight: 452455.88

Authors

Cao, D.,Ma, B.,Cao, Z.,Zhang, X.,Xiang, Y. (deposition date: 2024-12-15, release date: 2025-06-04, Last modification date: 2025-07-16)

Primary citation

Ma, B.,Cao, Z.,Ding, W.,Zhang, X.,Xiang, Y.,Cao, D.
Structural basis for the recognition of two different types of receptors by Western equine encephalitis virus.
Cell Rep, 44:115724-115724, 2025

PubMed Abstract: 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.

PubMed: 40402741
DOI: 10.1016/j.celrep.2025.115724

Experimental method

ELECTRON MICROSCOPY (3.3 Å)