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- EMDB-75816: Monoclonal antibodies A4, 7E8, and RVC68 in complex with rabies v... -

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Basic information

Entry
Database: EMDB / ID: EMD-75816
TitleMonoclonal antibodies A4, 7E8, and RVC68 in complex with rabies virus glycoprotein
Map data
Sample
  • Complex: Complex of RABV-G pre-fusion trimers with 7E8, A4, and RVC68 Fabs
KeywordsRabies / Rabies virus glycoprotein / antibody / VIRAL PROTEIN
Biological speciesLyssavirus rabies
Methodsingle particle reconstruction / cryo EM / Resolution: 3.83 Å
AuthorsCallaway HM / Zyla D / Hastie K / Harkins S / Kothalawalage S / Samarasinghe S / Flynn A / Hariharan C / Yin J / Corti D ...Callaway HM / Zyla D / Hastie K / Harkins S / Kothalawalage S / Samarasinghe S / Flynn A / Hariharan C / Yin J / Corti D / Bouhry H / Dessain S / Saphire EO
Funding support United States, 2 items
OrganizationGrant numberCountry
Other private United States
Other private United States
CitationJournal: Cell Rep / Year: 2026
Title: Antigenic landscape of rabies and related lyssaviruses revealed by cryo-EM.
Authors: Heather M Callaway / Dawid S Zyla / Kathryn M Hastie / Stephanie S Harkins / Shanika Kothalawalage / Nimasha Samarasinghe / Alexander Flynn / Chitra Hariharan / Jieyun Yin / Davide Corti / ...Authors: Heather M Callaway / Dawid S Zyla / Kathryn M Hastie / Stephanie S Harkins / Shanika Kothalawalage / Nimasha Samarasinghe / Alexander Flynn / Chitra Hariharan / Jieyun Yin / Davide Corti / Herve Bourhy / Scott K Dessain / Erica Ollmann Saphire /
Abstract: Rabies continues to kill over 60,000 people per year despite life-saving vaccines and post-exposure treatments and costs billions of dollars in prevention and treatment. Preventing rabies deaths and ...Rabies continues to kill over 60,000 people per year despite life-saving vaccines and post-exposure treatments and costs billions of dollars in prevention and treatment. Preventing rabies deaths and reducing the global economic burden of the virus will require both developing a monoclonal antibody cocktail to replace human serum in treatment and improving rabies vaccines to elicit long-lasting protection. Here, we solve nine cryo-electron microscopy (cryo-EM) structures of neutralizing monoclonal antibodies (mAbs) in complex with the rabies virus glycoprotein (RABV-G). The nine structures span three known antigenic sites plus two additional antigenic sites, not among the five classically identified sites. We find that these antigenic sites, V and VI, are broadly cross-reactive across lyssaviruses, whereas immunodominant sites II/IV and III are rabies specific. Across the mAb panel, fusion inhibition and binding affinity correlate best with neutralization. Together, these results provide a roadmap for structure-guided vaccine and therapeutic antibody design for rabies and related lyssaviruses.
History
DepositionMar 3, 2026-
Header (metadata) releaseAug 19, 2026-
Map releaseAug 19, 2026-
UpdateSep 30, 2026-
Current statusSep 30, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_75816.png

Downloads & links

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Map

FileDownload / File: emd_75816.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.32 Å/pix.
x 256 pix.
= 337.92 Å		1.32 Å/pix.
x 256 pix.
= 337.92 Å		1.32 Å/pix.
x 256 pix.
= 337.92 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.32 Å
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Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.108483985 - 0.39563403
Average (Standard dev.)0.0015920717 (±0.020038472)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 337.92 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_75816_half_map_1.map
Projections & Slices
AxesZYX

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Half map: #2

Fileemd_75816_half_map_2.map
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : Complex of RABV-G pre-fusion trimers with 7E8, A4, and RVC68 Fabs

EntireName: Complex of RABV-G pre-fusion trimers with 7E8, A4, and RVC68 Fabs
Components
  • Complex: Complex of RABV-G pre-fusion trimers with 7E8, A4, and RVC68 Fabs

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Supramolecule #1: Complex of RABV-G pre-fusion trimers with 7E8, A4, and RVC68 Fabs

SupramoleculeName: Complex of RABV-G pre-fusion trimers with 7E8, A4, and RVC68 Fabs
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Lyssavirus rabies

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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

Concentration0.15 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
137.0 mMNaClSodium chloride
27.0 mMKClPotassium Chloride
100.0 mMNa2HPO4Sodium Phosphate
18.0 mMKH2PO4Potassium Phosphate
GridModel: C-flat-2/1 / Support film - Material: CARBON / Support film - topology: HOLEY
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
SoftwareName: EPU
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
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: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.83 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 35178
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

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