9E96

WEEV CBA87 VLP in complex with human PCDH10-EC1

Summary for 9E96

• Entry DOI: 10.2210/pdb9e96/pdb
• EMDB information: 47775
• Descriptor: Structural polyprotein, Capsid protein, Protocadherin-10, ... (4 entities in total)
• Functional Keywords: alphavirus receptor, viral protein
• Biological source: Western equine encephalitis virus; More
• Total number of polymer chains: 16
• Total formula weight: 485274.62

Authors

Raju, S.,Diamond, M.S.,Fremont, D.H. (deposition date: 2024-11-07, release date: 2025-04-23)

Primary citation

Raju, S.,Palakurty, S.,Sariol, A.,Wagoner, N.,Adams, L.J.,Hui, S.,Klimstra, W.B.,Fremont, D.H.,Diamond, M.S.
Structural basis for plasticity in receptor engagement by an encephalitic alphavirus.
Cell, 2025

PubMed Abstract: The structural basis for shifts in receptor usage remains poorly understood despite the implications for virus adaptation and emergence. Western equine encephalitis virus (WEEV) strains exhibit different patterns of engagement for two of their entry receptors: very-low-density lipoprotein receptor (VLDLR) and protocadherin 10 (PCDH10). Using structural and functional studies, we show that while all WEEV strains have a lipoprotein class A (LA) domain binding site near the E1 fusion loop, VLDLR engagement requires a second binding site in E2 that can vary with single nucleotide substitutions. We also resolve a structure of PCDH10 bound to WEEV, which reveals interactions near the E1 fusion loop with residues that also mediate LA domain binding. Evolutionary analysis enabled the generation of a PCDH10 decoy that protects in vivo against all WEEV strains tested. Our experiments demonstrate how viruses can engage multiple receptors using shared determinants, which likely impacts cellular tropism and virulence.

PubMed: 40187344
DOI: 10.1016/j.cell.2025.02.036

Experimental method

ELECTRON MICROSCOPY (4.05 Å)