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- EMDB-74158: LDLRAD3-vLA1-VLDLR-LA2 in complex with EEEV PE-6 VLPs (ASU) -

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Basic information

Entry
Database: EMDB / ID: EMD-74158
TitleLDLRAD3-vLA1-VLDLR-LA2 in complex with EEEV PE-6 VLPs (ASU)
Map data
Sample
  • Virus: Eastern equine encephalitis virus
    • Complex: LDLRAD3-vLA1-VLDLR-LA2
KeywordsReceptor Decoy / VIRUS LIKE PARTICLE
Biological speciesHomo sapiens (human) / Eastern equine encephalitis virus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.22 Å
AuthorsRaju S / Diamond MS
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI143673 United States
CitationJournal: Sci Transl Med / Year: 2026
Title: Design of a neutralizing and protective pan-encephalitic alphavirus receptor decoy protein.
Authors: Sathvik Palakurty / Saravanan Raju / Alan Sariol / Ngan Wagoner / Theron C Gilliland / William B Klimstra / Michael S Diamond /
Abstract: Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are alphaviruses from different serocomplexes that cause neurological disease in humans. Given their antigenic ...Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are alphaviruses from different serocomplexes that cause neurological disease in humans. Given their antigenic distance, it has been challenging to isolate cross-reactive antibodies that neutralize infection by multiple medically relevant encephalitic alphaviruses. Recently, distinct entry receptors were identified for these encephalitic alphaviruses: LDLRAD3 for VEEV, VLDLR for EEEV and some strains of WEEV, and PCDH10 for WEEV. Here, using structure-guided mutagenesis, we generated a soluble chimeric protein derived from the LA1 domain of LDLRAD3 and the LA2 domain of VLDLR, termed LDLRAD3-vLA1-VLDLR-LA2, which neutralized infection by VEEV, EEEV, and some WEEV strains in cell culture and protected mice from infection. Structural analysis of this engineered decoy revealed binding to distinct sites on each virus, which corresponded to those engaged by their endogenous entry receptors. We extended the neutralizing and protective capacity to contemporary WEEV strains by adding a single extracellular cadherin domain from sparrow PCDH10 through a stabilized symmetric bispecific decoy scaffold. Our designed receptor decoy serves as a possible countermeasure against multiple encephalitic alphaviruses, and this design platform could be harnessed to develop therapeutic agents against viruses from other families.
History
DepositionDec 2, 2025-
Header (metadata) releaseApr 22, 2026-
Map releaseApr 22, 2026-
UpdateApr 22, 2026-
Current statusApr 22, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_74158.png

Downloads & links

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Map

FileDownload / File: emd_74158.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 300 pix.
= 324.3 Å		1.08 Å/pix.
x 300 pix.
= 324.3 Å		1.08 Å/pix.
x 300 pix.
= 324.3 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.081 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.4
Minimum - Maximum-2.1102376 - 2.8572516
Average (Standard dev.)0.0011322397 (±0.10247275)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 324.3 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_74158_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_74158_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : Eastern equine encephalitis virus

EntireName: Eastern equine encephalitis virus
Components
  • Virus: Eastern equine encephalitis virus
    • Complex: LDLRAD3-vLA1-VLDLR-LA2

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Supramolecule #1: Eastern equine encephalitis virus

SupramoleculeName: Eastern equine encephalitis virus / type: virus / ID: 1 / Parent: 0 / NCBI-ID: 11021 / Sci species name: Eastern equine encephalitis virus / Sci species strain: PE-6 / Virus type: VIRUS-LIKE PARTICLE / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: Yes

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Supramolecule #2: LDLRAD3-vLA1-VLDLR-LA2

SupramoleculeName: LDLRAD3-vLA1-VLDLR-LA2 / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 45.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 0.7000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 172425
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
FSC plot (resolution estimation)

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