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- EMDB-79039: Australian bat lyssavirus glycoprotein PH domain in complex with ... -

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Basic information

Entry
Database: EMDB / ID: EMD-79039
TitleAustralian bat lyssavirus glycoprotein PH domain in complex with broadly neutralizing human antibodies A6 and RVC20
Map data
Sample
  • Virus: Lyssavirus australis
    • Protein or peptide: Antibody RVC20 heavy chain
    • Protein or peptide: Antibody RVC20 light chain
    • Protein or peptide: Antibody A6 heavy chain
    • Protein or peptide: Antibody A6 light chain
    • Protein or peptide: Glycoprotein
KeywordsABVL / PHD / antibody / neutralizing / VIRAL PROTEIN
Function / homology: / Rhabdovirus glycoprotein G PH domain / : / Rhabdovirus spike glycoprotein G central domain / Rhabdovirus glycoprotein / Rhabdovirus spike glycoprotein fusion domain / viral envelope / virion membrane / Glycoprotein
Function and homology information
Biological speciesHomo sapiens (human) / Lyssavirus australis
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsXu K / Xu Y
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UH2AI171611 United States
CitationJournal: Emerg Microbes Infect / Year: 2026
Title: Peripheral human mAb therapy yields modulation of neuroinflammation and long-term functional recovery from lyssavirus infection.
Authors: Celeste Huaman / Yan Xu / Nathaniel M Lott / Elise M Santorella / Madeline Rader / Allison M Strazzella / Caitlyn Clouse / Jocelyn M King / Mattie Melnyk / Junping Hong / Lianying Yan / ...Authors: Celeste Huaman / Yan Xu / Nathaniel M Lott / Elise M Santorella / Madeline Rader / Allison M Strazzella / Caitlyn Clouse / Jocelyn M King / Mattie Melnyk / Junping Hong / Lianying Yan / Adrian C Paskey / Andrea E Luquette / Francisco Malagon / Regina Z Cer / Kimberly A Bishop-Lilly / Daniel P Perl / Christopher C Broder / Kai Xu / Brian C Schaefer /
Abstract: Rabies is a fatal encephalitis caused by viruses in the lyssavirus genus. We previously demonstrated that intraperitoneal administration of a single dose of neutralizing human monoclonal antibody ...Rabies is a fatal encephalitis caused by viruses in the lyssavirus genus. We previously demonstrated that intraperitoneal administration of a single dose of neutralizing human monoclonal antibody (mAb) F11 can protect mice from fatal lyssavirus infection, post-central nervous system (CNS) invasion. However, the molecular basis of F11 neutralization remains unknown. Here, we use structural and functional analyses to define neutralizing activity of F11 and the related mAb, A6. Cryo-electron microscopy (EM) and negative-stain EM reveal that both mAbs bind Domain III of the glycoprotein G, recognizing a prefusion-specific epitope distinct from previously characterized antibodies including RVC20. Binding stabilizes the prefusion state, blocking membrane fusion. We furthermore found that a single dose of either A6 or RVC20 protected animals from mortality induced by Australian bat lyssavirus (ABLV), while promoting substantial long-term functional recovery. Moreover, A6 similarly protected animals from mortality following infection with a currently circulating wild isolate of rabies virus (RABV). Transcriptomics analysis of brain RNA and protein-based analysis of brain tissue homogenates demonstrated that therapy with A6 broadly reduced expression of neuroinflammatory mediators during the acute phase of infection. Interestingly, infection of animals with a non-lethal attenuated mutant of ABLV resulted in similar neuroinflammation. Thus, a robust neuroinflammatory response to ABLV does not predict mortality. Overall, peripheral therapy with A6 and similar neutralizing mAbs promotes survival and long-term functional recovery from CNS-resident lyssavirus infection in a manner that includes suppression of the G pre- to postfusion transition and modulation of neuroinflammation.
History
DepositionSep 11, 2026-
Header (metadata) releaseSep 30, 2026-
Map releaseSep 30, 2026-
UpdateSep 30, 2026-
Current statusSep 30, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_79039.png

Downloads & links

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Map

FileDownload / File: emd_79039.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 360 pix.
= 306.72 Å		0.85 Å/pix.
x 360 pix.
= 306.72 Å		0.85 Å/pix.
x 360 pix.
= 306.72 Å

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.852 Å
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Histogram (log scale)
Contour LevelBy AUTHOR: 0.15
Minimum - Maximum0.0 - 0.68705726
Average (Standard dev.)0.0014742952 (±0.010957737)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 306.72 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_79039_msk_1.map
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Additional map: #1

Fileemd_79039_additional_1.map
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Half map: #2

Fileemd_79039_half_map_1.map
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Half map: #1

Fileemd_79039_half_map_2.map
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Sample components

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Entire : Lyssavirus australis

EntireName: Lyssavirus australis
Components
  • Virus: Lyssavirus australis
    • Protein or peptide: Antibody RVC20 heavy chain
    • Protein or peptide: Antibody RVC20 light chain
    • Protein or peptide: Antibody A6 heavy chain
    • Protein or peptide: Antibody A6 light chain
    • Protein or peptide: Glycoprotein

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Supramolecule #1: Lyssavirus australis

SupramoleculeName: Lyssavirus australis / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 90961 / Sci species name: Lyssavirus australis / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No

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Macromolecule #1: Antibody RVC20 heavy chain

MacromoleculeName: Antibody RVC20 heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.627051 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLQESGPG LVKPSQTLSL TCTVSGGSFS SGSYSWNWIR QHPGKGLEWI GYIYYSGSTY YNPSLKSRVT MSVHTSKNQF SLKLNSITA ADTAVYYCAR GTYSDFWSGS PLDYWGQGTL VTVSS

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Macromolecule #2: Antibody RVC20 light chain

MacromoleculeName: Antibody RVC20 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.523791 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
DIQMTQSPSS LSASVGDRVT ITCRASQGIS NYLAWFQQKP GKAPKSLIYA ASSLQSGVPS RFSGSGSGTD FTLTINSLQP EDFVTYFCQ QYDTYPLTFG GGTKVEIK

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Macromolecule #3: Antibody A6 heavy chain

MacromoleculeName: Antibody A6 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 14.091765 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVQSGAE VKKPGASVKV SCKASGYDFT DFYVHWVRQA PGQRLEWMGW INPGSGATDY AQKFQGRVTM TRDTSISTAY MEVSRLRSD DTAMYYCARP NAPRYMERLS ATPSFDSWGQ GTLVTVS

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Macromolecule #4: Antibody A6 light chain

MacromoleculeName: Antibody A6 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 11.441696 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EIVLTQSPGT LSLSPGEGAT LSCRASQSVS SINLAWYQQK PGQAPRLLMY GASTRATGIP DRFSGSGSGT DFTLTISRLE SEDFAVYYC QQYGSSPLTF GGGTKVEIK

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Macromolecule #5: Glycoprotein

MacromoleculeName: Glycoprotein / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lyssavirus australis
Molecular weightTheoretical: 10.483997 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
NLIVEDEGCT SLSGFSYMEL KGGGGSGGGG SSCDIFTMSK GKKASKGGKV CGFVDERGLY KSLKGACKLK LCGISGLRLL DGSWVSIQN HEEVKWCSPN Q

UniProtKB: Glycoprotein, Glycoprotein

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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

Concentration1 mg/mL
BufferpH: 7.2 / Details: 5mM HEPES buffer pH7.2, 150nM NaCl
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 273 K / Instrument: FEI VITROBOT MARK IV
Details1mg/ml in HBS buffer, purfied from HEK293 recombinant expression and purified with NiNTA resin via Hisx6 tag

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Electron microscopy

MicroscopeTFS KRIOS
SoftwareName: EPU
Image recordingFilm or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsCalibrated defocus max: 30.0 µm / Calibrated defocus min: 1.5 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 25.0 µm / Nominal defocus min: 8.0 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: PDB ENTRY
PDB model - PDB ID:

6tou

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3) / Number images used: 195885
Initial angle assignmentType: OTHER
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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