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- EMDB-48677: D1 Herpes Virus Simplex Neutralizing Nanobody Bound to HSV Glycop... -

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Basic information

Entry
Database: EMDB / ID: EMD-48677
TitleD1 Herpes Virus Simplex Neutralizing Nanobody Bound to HSV Glycoprotein gB
Map data
Sample
  • Complex: One D1 Neutralizing Nanobody bound to each monomer of the HSV Glycoprotein B Trimer
    • Protein or peptide: Envelope glycoprotein B
    • Protein or peptide: D1 Neutralizing Nanobody
  • Ligand: SODIUM ION
  • Ligand: water
KeywordsNeutralizing Antibody / ANTIVIRAL PROTEIN
Function / homology
Function and homology information


host cell Golgi membrane / host cell endosome membrane / viral envelope / symbiont entry into host cell / virion attachment to host cell / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
: / Herpesvirus Glycoprotein B / Herpesvirus Glycoprotein B, PH-like domain 1 / Herpesvirus Glycoprotein B, PH-like domain 2 / Herpesvirus Glycoprotein B, PH-like domain 2 superfamily / Herpesvirus Glycoprotein B ectodomain / Herpesvirus Glycoprotein B / Herpesvirus Glycoprotein B PH-like domain
Similarity search - Domain/homology
Envelope glycoprotein B
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.1 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 16, 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_48677.png

Downloads & links

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Map

FileDownload / File: emd_48677.map.gz / Format: CCP4 / Size: 178 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 360 pix.
= 262.44 Å		0.73 Å/pix.
x 360 pix.
= 262.44 Å		0.73 Å/pix.
x 360 pix.
= 262.44 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: 0.14
Minimum - Maximum-0.8159076 - 1.449624
Average (Standard dev.)0.00064667506 (±0.0418404)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 262.44 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_48677_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_48677_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 : One D1 Neutralizing Nanobody bound to each monomer of the HSV Gly...

EntireName: One D1 Neutralizing Nanobody bound to each monomer of the HSV Glycoprotein B Trimer
Components
  • Complex: One D1 Neutralizing Nanobody bound to each monomer of the HSV Glycoprotein B Trimer
    • Protein or peptide: Envelope glycoprotein B
    • Protein or peptide: D1 Neutralizing Nanobody
  • Ligand: SODIUM ION
  • Ligand: water

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Supramolecule #1: One D1 Neutralizing Nanobody bound to each monomer of the HSV Gly...

SupramoleculeName: One D1 Neutralizing Nanobody bound to each monomer of the HSV Glycoprotein B Trimer
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Details: There are 6 molecules in the complex. A trimer of HSV Glycoprotein B and one D1 Neutralizing Nanobody bound to each Glycoprotein B monomer.
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Envelope glycoprotein B

MacromoleculeName: Envelope glycoprotein B / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 82.052039 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: APAAPAAPRA SGGVAATVAA NGGPASRPPP VPSPATTKAR KRKTKKPPKR PEATPPPDAN ATVAAGHATL RAHLREIKVE NADAQFYVC PPPTGATVVQ FEQPRRCPTR PEGQNYTEGI AVVFKENIAP YKFKATMYYK DVTVSQVWFG HRYSQFMGIF E DRAPVPFE ...String:
APAAPAAPRA SGGVAATVAA NGGPASRPPP VPSPATTKAR KRKTKKPPKR PEATPPPDAN ATVAAGHATL RAHLREIKVE NADAQFYVC PPPTGATVVQ FEQPRRCPTR PEGQNYTEGI AVVFKENIAP YKFKATMYYK DVTVSQVWFG HRYSQFMGIF E DRAPVPFE EVIDKINAKG VCRSTAKYVR NNMETTAFHR DDHETDMELK PAKVATRTSR GWHTTDLKYN PSRVEAFHRY GT TVNCIVE EVDARSVYPY DEFVLATGDF VYMSPFYGYR EGSHTEHTSY AADRFKQVDG FYARDLTTKA RATSPTTRNL LTT PKFTVA WDWVPKRPAV CTMTKWQEVD EMLRAEYGGS FRFSSDAIST TFTTNLTEYS LSRVDLGDCI GRDAREAIDR MFAR KYNAT HIKVGQPQYY LATGGFLIAY QPLLSNTLAE LYVREYMREQ DRKPRNATPA PLREAPSANA SVERIKTTSS IEFAR LQFT YNHIQRHVND MLGRIAVAWC ELQNHELTLW NEARKLNPNA IASATVGRRV SARMLGDVMA VSTCVPVAPD NVIVQN SMR VSSRPGTCYS RPLVSFRYED QGPLIEGQLG ENNELRLTRD ALEPCTVGHR RYFIFGGGYV YFEEYAYSHQ LSRADVT TV STFIDLNITM LEDHEFVPLE VYTRHEIKDS GLLDYTEVQR RNQLHDLRFA DIDTVIRADA NAAGGGSHHH HHHHHGSD Y KDDDDK

UniProtKB: Envelope glycoprotein B

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Macromolecule #2: D1 Neutralizing Nanobody

MacromoleculeName: D1 Neutralizing Nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 14.454935 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLLESGGG LVQPGGSLRL SCAASGRGFS MLNVGWFRQA PGKGREFVAT ISWTGERTYY GDSVKGRFTI SRDNSKNTAY LQMNSLRAE DTAVYYCAAV GPKTWDYGLA SEYDYWGQGT QVTVSSHHHH HH

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Macromolecule #3: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 3 / Number of copies: 6
Molecular weightTheoretical: 22.99 Da

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Macromolecule #4: water

MacromoleculeName: water / type: ligand / ID: 4 / Number of copies: 5516 / 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

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionNumber classes used: 39 / Applied symmetry - Point group: C3 (3 fold cyclic) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 2.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 182131
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
FSC plot (resolution estimation)

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