EMD-42193

Single-particle
4.21 Å
EMD-42193 Deposition: 04/10/2023
Map released: 14/02/2024
Last modified: 14/02/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-42193

Eastern equine encephalitis virus (PE-6) VLP in complex with VLDLR LA(1-3) (icosahedral)

EMD-42193

Single-particle
4.21 Å
EMD-42193 Deposition: 04/10/2023
Map released: 14/02/2024
Last modified: 14/02/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Eastern equine encephalitis virus
Sample: Eastern equine encephalitis virus

Deposition Authors: Adams LJ , Fremont DH
Structural and functional basis of VLDLR usage by Eastern equine encephalitis virus.
Adams LJ , Raju S, Ma H, Gilliland Jr T, Reed DS, Klimstra WB, Fremont DH , Diamond MS
(2024) Cell , 187 , 360 - 374.e19
PUBMED: 38176410
DOI: doi:10.1016/j.cell.2023.11.031
ISSN: 1097-4172
Abstract:
The very-low-density lipoprotein receptor (VLDLR) comprises eight LDLR type A (LA) domains and supports entry of distantly related alphaviruses, including Eastern equine encephalitis virus (EEEV) and Semliki Forest virus (SFV). Here, by resolving multiple cryo-electron microscopy structures of EEEV-VLDLR complexes and performing mutagenesis and functional studies, we show that EEEV uses multiple sites (E1/E2 cleft and E2 A domain) to engage more than one LA domain simultaneously. However, no single LA domain is necessary or sufficient to support efficient EEEV infection. Whereas all EEEV strains show conservation of two VLDLR-binding sites, the EEEV PE-6 strain and a few other EEE complex members feature a single amino acid substitution that enables binding of LA domains to an additional site on the E2 B domain. These structural and functional analyses informed the design of a minimal VLDLR decoy receptor that neutralizes EEEV infection and protects mice from lethal challenge.