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TitleStructural basis for the recognition of two different types of receptors by Western equine encephalitis virus.
Journal, issue, pagesCell Rep, Vol. 44, Issue 6, Page 115724, Year 2025
Publish dateMay 20, 2025
AuthorsBingting Ma / Ziyi Cao / Weijia Ding / Xinzheng Zhang / Ye Xiang / Duanfang Cao /
PubMed AbstractWestern 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.
External linksCell Rep / PubMed:40402741
MethodsEM (single particle)
Resolution3.3 - 4.9 Å
Structure data

62749

9l1n

EMDB-62749, PDB-9l1n:
Structure of Western equine encephalitis virus 71V1658 strain VLP in complex with human PCDH10 EC1
Method: EM (single particle) / Resolution: 3.3 Å

62898

9l99

EMDB-62898, PDB-9l99:
Structure of Western equine encephalitis virus McMillan strain in complex with VLDLR LA1-2
Method: EM (single particle) / Resolution: 3.6 Å

62899

9l9a

EMDB-62899, PDB-9l9a:
Structure of Western equine encephalitis virus McMillan strain in complex with VLDLR LA2-3
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-63653: Western equine encephalitis virus 71V1658 strain VLP in complex with human PCDH10 EC1-6
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-63654: Western equine encephalitis virus McMillan strain in complex with VLDLR LA1-8
Method: EM (single particle) / Resolution: 4.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CA:
Unknown entry

Source
  • western equine encephalitis virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Western Equine Encephalitis virus / WEEV / PCDH10 / EC1 / receptor / complex / glycoprotein / VLDLR / McMillan strain / LA1-2 / LA2-3

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