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- EMDB-75813: Human monoclonal antibodies 4C12 and 4H3 in complex with rabies v... -

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Basic information

Entry
Database: EMDB / ID: EMD-75813
TitleHuman monoclonal antibodies 4C12 and 4H3 in complex with rabies virus glycoprotein
Map data
Sample
  • Complex: Complex of RABV-G pre-fusion trimers with RVA122, 4C12, and 4H3 Fabs
    • Protein or peptide: Monoclonal Antibody RVA122 Light Chain
    • Protein or peptide: Monoclonal Antibody RVA122 Heavy Chain
    • Protein or peptide: Glycoprotein
    • Protein or peptide: Monoclonal Antibody 4H3 Light Chain
    • Protein or peptide: Monoclonal Antibody 4C12 Light Chain
    • Protein or peptide: Monoclonal Antibody 4H3 Heavy Chain
    • Protein or peptide: Monoclonal Antibody 4C12 Heavy Chain
KeywordsRabies / Rabies virus glycoprotein / antibody / VIRAL PROTEIN
Function / homology
Function and homology information


viral membrane / entry receptor-mediated virion attachment to host cell / fusion of virus membrane with host endosome membrane / viral envelope / virion membrane
Similarity search - Function
: / Rhabdovirus glycoprotein G PH domain / : / Rhabdovirus spike glycoprotein G central domain / Rhabdovirus glycoprotein / Rhabdovirus spike glycoprotein fusion domain
Similarity search - Domain/homology
Biological speciesLyssavirus rabies / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.24 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_75813.png

Downloads & links

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Map

FileDownload / File: emd_75813.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 400 pix.
= 440. Å		1.1 Å/pix.
x 400 pix.
= 440. Å		1.1 Å/pix.
x 400 pix.
= 440. Å

Surface

Projections

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.22427922 - 0.62313
Average (Standard dev.)0.00006998657 (±0.016740324)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 440.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_75813_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_75813_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 RVA122, 4C12, and 4H3 Fabs

EntireName: Complex of RABV-G pre-fusion trimers with RVA122, 4C12, and 4H3 Fabs
Components
  • Complex: Complex of RABV-G pre-fusion trimers with RVA122, 4C12, and 4H3 Fabs
    • Protein or peptide: Monoclonal Antibody RVA122 Light Chain
    • Protein or peptide: Monoclonal Antibody RVA122 Heavy Chain
    • Protein or peptide: Glycoprotein
    • Protein or peptide: Monoclonal Antibody 4H3 Light Chain
    • Protein or peptide: Monoclonal Antibody 4C12 Light Chain
    • Protein or peptide: Monoclonal Antibody 4H3 Heavy Chain
    • Protein or peptide: Monoclonal Antibody 4C12 Heavy Chain

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Supramolecule #1: Complex of RABV-G pre-fusion trimers with RVA122, 4C12, and 4H3 Fabs

SupramoleculeName: Complex of RABV-G pre-fusion trimers with RVA122, 4C12, and 4H3 Fabs
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Lyssavirus rabies

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Macromolecule #1: Monoclonal Antibody RVA122 Light Chain

MacromoleculeName: Monoclonal Antibody RVA122 Light Chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.44983 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: QSVLTQSPSA SDTPGQRVTI SCSGSSSNIG SNYVYWYQQF PGTAPKLLIY KSDKRPSGVP DRFSGSTSGT SASLAISGLR SEDEADYYC AAWDNRLSGW LFGGGTKLTV LGTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS G NSQESVTE ...String:
QSVLTQSPSA SDTPGQRVTI SCSGSSSNIG SNYVYWYQQF PGTAPKLLIY KSDKRPSGVP DRFSGSTSGT SASLAISGLR SEDEADYYC AAWDNRLSGW LFGGGTKLTV LGTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS G NSQESVTE QDSKDSTYSL SSTLTLSKAD YEKHKVYACE VTHQGLRSPV TKSFNRGEC

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Macromolecule #2: Monoclonal Antibody RVA122 Heavy Chain

MacromoleculeName: Monoclonal Antibody RVA122 Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.196096 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: QVHLQESGPG LVKPSETLSL TCTVSGDSMN NFYWGWIRQP AGKGLEWIGY IYYSGTTNYN PSLKSRVTIS IDTSKNQFSL KVNSVTAAD TAVYYCARDS GDYVSYYYYG MDVWGPGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String:
QVHLQESGPG LVKPSETLSL TCTVSGDSMN NFYWGWIRQP AGKGLEWIGY IYYSGTTNYN PSLKSRVTIS IDTSKNQFSL KVNSVTAAD TAVYYCARDS GDYVSYYYYG MDVWGPGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDL EVDDDDKAGW SH PQFEKGG GSGGGSGGGS WSHPQFEK

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Macromolecule #3: Glycoprotein

MacromoleculeName: Glycoprotein / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Lyssavirus rabies
Molecular weightTheoretical: 52.204164 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: KFPIYTIPDK LGPWSPIDIH HLSCPNNLVV EDEGCTNLSG FSYMELKVGY ISAIKMNGFT CTGVVTEAET YTNFVGYVTT TFKRKHFRP TPDACRAAYN WKMAGDPRYE ESLHNPYPDY HWLRTVKTTK ESLVIISPSV ADLDPYDRSL HSRVFPGGNC S GVAVSSTY ...String:
KFPIYTIPDK LGPWSPIDIH HLSCPNNLVV EDEGCTNLSG FSYMELKVGY ISAIKMNGFT CTGVVTEAET YTNFVGYVTT TFKRKHFRP TPDACRAAYN WKMAGDPRYE ESLHNPYPDY HWLRTVKTTK ESLVIISPSV ADLDPYDRSL HSRVFPGGNC S GVAVSSTY CSTNHDYTIW MPENPRLGMS CDIFTNSRGK RASKGSETCG FVDERGLYKS LKGACKLKLC GVLGLRLMDG TW VAMQTSN ETKWCPPGQL VNLHDFRSDE IEHLVVEELV KKREECLDAL ESIMTTKSVS FRRLSHLRKL VPGFGKAYTI FNK TLMEAD AHYKSVRTWN EIIPSKGCLR VGGRCHPHVN GVFFNGIILG PDGNVLIPEM QSSLLQQHME LLVSSVIPLM HPLA DPSTV FKNGDEAEDF VEVHLGWSHP QFEKGGGSGG GSGGGSWSHP QFEKGSGSGL NDIFEAQKIE WHE

UniProtKB: Glycoprotein

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Macromolecule #4: Monoclonal Antibody 4H3 Light Chain

MacromoleculeName: Monoclonal Antibody 4H3 Light Chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.911277 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNPVNWYQQL PGTAPKLLIY NNDQRPSGVP GRFSGSKSGT SASLEIRGLQ SEDEADYYC AAWHDSLNGW VFGGGTKLTV LGQPKANPTV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADGSPV K AGVETTKP ...String:
QSVLTQPPSA SGTPGQRVTI SCSGSSSNIG SNPVNWYQQL PGTAPKLLIY NNDQRPSGVP GRFSGSKSGT SASLEIRGLQ SEDEADYYC AAWHDSLNGW VFGGGTKLTV LGQPKANPTV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADGSPV K AGVETTKP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS

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Macromolecule #5: Monoclonal Antibody 4C12 Light Chain

MacromoleculeName: Monoclonal Antibody 4C12 Light Chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.830113 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: QSVLTQPPSA SATPGQRVTI SCSGSSSNVG SNTVDWYQQV PGTAPRLLIY GHNQRPSGVP DRFSNSQSGT SASLAISGLQ SGDEADYYC AVWDDSLTAW LFGGGTKLTV LGQPKANPTV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADGSPV K AGVETTKP ...String:
QSVLTQPPSA SATPGQRVTI SCSGSSSNVG SNTVDWYQQV PGTAPRLLIY GHNQRPSGVP DRFSNSQSGT SASLAISGLQ SGDEADYYC AVWDDSLTAW LFGGGTKLTV LGQPKANPTV TLFPPSSEEL QANKATLVCL ISDFYPGAVT VAWKADGSPV K AGVETTKP SKQSNNKYAA SSYLSLTPEQ WKSHRSYSCQ VTHEGSTVEK TVAPTECS

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Macromolecule #6: Monoclonal Antibody 4H3 Heavy Chain

MacromoleculeName: Monoclonal Antibody 4H3 Heavy Chain / type: protein_or_peptide / ID: 6 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.566633 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: QVRLVQSGAE MKKPGASVRV SCEASGYTFT DYYIHWVRQA PGQGLDYMGW MNPSSGIAIY APKFQGRVTM TRDTSISAAY MDLSRLRSD DTAIYYCARL YYYVSGSYWD DSDYWGQGTL VSVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String:
QVRLVQSGAE MKKPGASVRV SCEASGYTFT DYYIHWVRQA PGQGLDYMGW MNPSSGIAIY APKFQGRVTM TRDTSISAAY MDLSRLRSD DTAIYYCARL YYYVSGSYWD DSDYWGQGTL VSVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD LEVDDDDKAG WS HPQFEKG GGSGGGSGGG SWSHPQFEK

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Macromolecule #7: Monoclonal Antibody 4C12 Heavy Chain

MacromoleculeName: Monoclonal Antibody 4C12 Heavy Chain / type: protein_or_peptide / ID: 7 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.76667 KDa
Recombinant expressionOrganism: Drosophila melanogaster (fruit fly)
SequenceString: QVQLQESGPG LVKPSETLSL TCTVSGGSID SYYWSWVRQP PGKGLEWIGY IFYSGSTTYN PSLNSRVSIS VDTSKNQFSL HLSSVTAAD TAVYYCARVV NHYYESGGRY IHAEYFQYWG QGTLVAVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String:
QVQLQESGPG LVKPSETLSL TCTVSGGSID SYYWSWVRQP PGKGLEWIGY IFYSGSTTYN PSLNSRVSIS VDTSKNQFSL HLSSVTAAD TAVYYCARVV NHYYESGGRY IHAEYFQYWG QGTLVAVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDLEVDDD DK AGWSHPQ FEKGGGSGGG SGGGSWSHPQ FEK

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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: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 262318
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

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