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- EMDB-48730: D7 Herpes Virus Simplex Neutralizing Nanobody Bound to HSV Glycop... -

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Basic information

Entry
Database: EMDB / ID: EMD-48730
TitleD7 Herpes Virus Simplex Neutralizing Nanobody Bound to HSV Glycoprotein gD
Map data
Sample
  • Complex: D7 Neutralizing Nanobody bound to the HSV Glycoprotein D
    • Protein or peptide: Anti-Nb Fab Heavy chain
    • Protein or peptide: Ig-like domain-containing protein
    • Protein or peptide: D7 Neutralizing Nanobody against HSV Glycoprotein D
    • Protein or peptide: Glycoprotein D
  • Ligand: water
KeywordsNeutralizing Antibody / ANTIVIRAL PROTEIN
Function / homology
Function and homology information


immunoglobulin complex / adaptive immune response / viral envelope / virion membrane / extracellular region / membrane / plasma membrane
Similarity search - Function
Herpesvirus glycoprotein D/GG/GX domain / Herpesvirus glycoprotein D/GG/GX domain / : / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin subtype / Immunoglobulin ...Herpesvirus glycoprotein D/GG/GX domain / Herpesvirus glycoprotein D/GG/GX domain / : / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Glycoprotein D / Ig-like domain-containing protein
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama) / Human herpesvirus 2
Methodsingle particle reconstruction / cryo EM / Resolution: 2.3 Å
AuthorsViadiu H / Abernathy E / Lee CV / Hung M / Yu Y / Xing W / Yu X
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Rep / Year: 2025
Title: Identification and engineering of potent bispecific antibodies that protect against herpes simplex virus recurrent disease.
Authors: Chingwei V Lee / Hector Viadiu / Apurva Kalamkar / David I Bernstein / Andrew Pae / Xinchao Yu / Sylvia Wong / Fernando J Bravo / Sheng Ding / Elbert Seto / Magdeleine Hung / Yu Yu / Weimei ...Authors: Chingwei V Lee / Hector Viadiu / Apurva Kalamkar / David I Bernstein / Andrew Pae / Xinchao Yu / Sylvia Wong / Fernando J Bravo / Sheng Ding / Elbert Seto / Magdeleine Hung / Yu Yu / Weimei Xing / Giuseppe A Papalia / Wei Kan / Brian Carr / Majlinda Thomas / Leah Tong / Priyanka Desai / Nadine Jarrousse / Alexandre Mercier / Meghan M Holdorf / Simon P Fletcher / Emma Abernathy /
Abstract: Herpes simplex virus (HSV) causes lifelong infections, including oral and genital herpes. There is no vaccine, and current antivirals are only partially effective at reducing symptoms and ...Herpes simplex virus (HSV) causes lifelong infections, including oral and genital herpes. There is no vaccine, and current antivirals are only partially effective at reducing symptoms and transmission. Therapeutic antibodies offer a potentially long-acting treatment option, although efforts to pursue this have been limited. We performed an alpaca immunization campaign and discovered high-affinity antibodies that both neutralized and completely blocked cell-to-cell spread (CCS), a key mechanism by which HSV evades neutralizing antibodies. Unexpectedly, we found that engineering antibodies into a bispecific format targeting two viral glycoproteins dramatically increased antiviral potency. Solving the structures of three antibodies using cryo-electron microscopy (cryo-EM) revealed a mechanistic understanding of how the bispecific format could enhance potency. Lastly, these bispecific antibodies significantly reduced lesion development in the guinea pig model of genital herpes, demonstrating that delayed dosing after latency establishment can reduce disease and confirming their potential as a transformative treatment option.
History
DepositionJan 21, 2025-
Header (metadata) releaseAug 13, 2025-
Map releaseAug 13, 2025-
UpdateAug 13, 2025-
Current statusAug 13, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_48730.png

Downloads & links

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Map

FileDownload / File: emd_48730.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 320 pix.
= 233.28 Å		0.73 Å/pix.
x 320 pix.
= 233.28 Å		0.73 Å/pix.
x 320 pix.
= 233.28 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.729 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.06
Minimum - Maximum-0.72315675 - 0.92928773
Average (Standard dev.)0.000035820718 (±0.014707955)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 233.28 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_48730_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_48730_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : D7 Neutralizing Nanobody bound to the HSV Glycoprotein D

EntireName: D7 Neutralizing Nanobody bound to the HSV Glycoprotein D
Components
  • Complex: D7 Neutralizing Nanobody bound to the HSV Glycoprotein D
    • Protein or peptide: Anti-Nb Fab Heavy chain
    • Protein or peptide: Ig-like domain-containing protein
    • Protein or peptide: D7 Neutralizing Nanobody against HSV Glycoprotein D
    • Protein or peptide: Glycoprotein D
  • Ligand: water

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Supramolecule #1: D7 Neutralizing Nanobody bound to the HSV Glycoprotein D

SupramoleculeName: D7 Neutralizing Nanobody bound to the HSV Glycoprotein D
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Details: There are 4 molecules in the complex. A HSV Glycoprotein D monomer neutrilized by the D7 Nanobody and one tool Fab to enable CryoEM studies (light and heavy chains).
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Anti-Nb Fab Heavy chain

MacromoleculeName: Anti-Nb Fab Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 26.328123 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVESGGG LVQPGGSLRL SCAASGFNFS YYSIHWVRQA PGKGLEWVAY ISSSSSYTSY ADSVKGRFTI SADTSKNTAY LQMNSLRAE DTAVYYCARG YQYWQYHASW YWNGGLDYWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String:
EVQLVESGGG LVQPGGSLRL SCAASGFNFS YYSIHWVRQA PGKGLEWVAY ISSSSSYTSY ADSVKGRFTI SADTSKNTAY LQMNSLRAE DTAVYYCARG YQYWQYHASW YWNGGLDYWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSCDKTHTGS HH HHHH

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Macromolecule #2: Ig-like domain-containing protein

MacromoleculeName: Ig-like domain-containing protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 23.171703 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QSSSSLITFG QGTKVEIKRT VAAPSVFIFP PSDSQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String:
DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QSSSSLITFG QGTKVEIKRT VAAPSVFIFP PSDSQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC

UniProtKB: Ig-like domain-containing protein

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Macromolecule #3: D7 Neutralizing Nanobody against HSV Glycoprotein D

MacromoleculeName: D7 Neutralizing Nanobody against HSV Glycoprotein D / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 13.588184 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVESGGG LVQPGGSLRL SCSASGSIPS IWIMYWYRQA PGKGRELVAQ ITNFGTTVYA DSVKGRFTIS SDASKNTVYL QMNSLRAED TAVYYCNLDV TLGPSRGAYW GKGTPVTVSS HHHHHH

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Macromolecule #4: Glycoprotein D

MacromoleculeName: Glycoprotein D / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human herpesvirus 2
Molecular weightTheoretical: 36.577203 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: KYALADPSLK MADPNRFRGK NLPVLDQLTD PPGVKRVYHI QPSLEDPFQP PSIPITVYYA VLERACRSVL LHAPSEAPQI VRGASDEAR KHTYNLTIAW YRMGDNCAIP ITVMEYTECP YNKSLGVCPI RTQPRWSYYD SFSAVSEDNL GFLMHAPAFE T AGTYLRLV ...String:
KYALADPSLK MADPNRFRGK NLPVLDQLTD PPGVKRVYHI QPSLEDPFQP PSIPITVYYA VLERACRSVL LHAPSEAPQI VRGASDEAR KHTYNLTIAW YRMGDNCAIP ITVMEYTECP YNKSLGVCPI RTQPRWSYYD SFSAVSEDNL GFLMHAPAFE T AGTYLRLV KINDWTEITQ FILEHRARAS CKYALPLRIP PAACLTSKAY QQGVTVDSIG MLPRFIPENQ RTVALYSLKI AG WHGPKPP YTSTLLPPEL SDTTNATQPE LVPEDPEDSA LLEDPAGTVS SQIPPNWHIP SIQDVAPHGG GSHHHHHHHH GSD YKDDDD K

UniProtKB: Glycoprotein D

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Macromolecule #5: water

MacromoleculeName: water / type: ligand / ID: 5 / Number of copies: 1489 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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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

Concentration2 mg/mL
BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 120 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
TemperatureMin: 83.0 K / Max: 83.0 K
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 52.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 50.0 µm / Calibrated defocus max: 1.5 µm / Calibrated defocus min: 0.6 µm / Calibrated magnification: 165000 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 165000
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

Particle selectionNumber selected: 4900000
CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionNumber classes used: 128 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 228770
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC

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