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- EMDB-70623: Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A... -

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Basic information

Entry
Database: EMDB / ID: EMD-70623
TitleHepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A and HEPC74
Map data
Sample
  • Complex: Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A and HEPC74
KeywordsHCV / E1E2 heterodimer / neutralizing antibody / vaccine antigen / VIRAL PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.3 Å
AuthorsJanus BM / Gonzalez FG / Ofek G
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI168048 United States
CitationJournal: Nat Commun / Year: 2026
Title: Native-like soluble E1E2 glycoprotein heterodimers on self-assembling protein nanoparticles for hepatitis C virus vaccine design.
Authors: Linling He / Yi-Zong Lee / Yi-Nan Zhang / Maddy L Newby / Benjamin M Janus / Fabrizio G Gonzalez / Garrett Ward / Connor DesRoberts / Shr-Hau Hung / Erick Giang / Joel D Allen / Liudmila ...Authors: Linling He / Yi-Zong Lee / Yi-Nan Zhang / Maddy L Newby / Benjamin M Janus / Fabrizio G Gonzalez / Garrett Ward / Connor DesRoberts / Shr-Hau Hung / Erick Giang / Joel D Allen / Liudmila Kulakova / Eric A Toth / Thomas R Fuerst / Mansun Law / Gilad Ofek / Max Crispin / Jiang Zhu /
Abstract: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. Development of an E1E2-based HCV vaccine has been hindered by the difficulty of ...Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. Development of an E1E2-based HCV vaccine has been hindered by the difficulty of producing a soluble E1E2 (sE1E2) antigen that faithfully recapitulates the native virion-associated heterodimer. Guided by cryo-electron microscopy (cryo-EM) structures, we engineer genotype 1a H77 sE1E2 by truncating the E1 and E2 stems (Cut), deleting a putative fusion peptide-containing region in E1 (Cut), and stabilizing the heterodimer using diverse scaffolds. All H77 sE1E2.Cut scaffolds exhibit native-like E1-E2 association and strong binding to the broadly neutralizing antibody (bNAb) AR4A. A genotype 1a HCV-1 sE1E2.Cut variant scaffolded by a modified SpyTag/SpyCatcher (SPYΔN) is selected for in vitro and in vivo characterization, as well as further construct refinement. The structure of this HCV-1 sE1E2 construct in complex with bNAbs is determined by cryo-EM and negative-stain EM (nsEM), with an nsEM-based strategy established for antibody epitope mapping. HCV-1 sE1E2.Cut.SPYΔN is displayed on self-assembling protein nanoparticles (SApNPs) to enhance immunogenicity. The HCV-1 sE1E2.Cut.SPYΔN heterodimer and SApNPs bearing wildtype or modified glycans are evaluated in mice, alongside E2 core-based immunogens for comparison. Together, these results establish a framework for advancing E1E2-based HCV vaccines toward clinical development.
History
DepositionMay 14, 2025-
Header (metadata) releaseFeb 4, 2026-
Map releaseFeb 4, 2026-
UpdateApr 1, 2026-
Current statusApr 1, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_70623.png

Downloads & links

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Map

FileDownload / File: emd_70623.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

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Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.53 Å/pix.
x 200 pix.
= 305.2 Å		1.53 Å/pix.
x 200 pix.
= 305.2 Å		1.53 Å/pix.
x 200 pix.
= 305.2 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.526 Å
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Contour LevelBy AUTHOR: 0.14
Minimum - Maximum-1.0884022 - 1.4327213
Average (Standard dev.)0.00039625578 (±0.030589137)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions200200200
Spacing200200200
CellA=B=C: 305.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_70623_half_map_1.map
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Half map: #1

Fileemd_70623_half_map_2.map
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Sample components

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Entire : Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A...

EntireName: Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A and HEPC74
Components
  • Complex: Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A and HEPC74

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Supramolecule #1: Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A...

SupramoleculeName: Hepatitis C virus sE1E2.Cut1+2.SPYdeltaN bound to antibodies AR4A and HEPC74
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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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

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.5 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 6.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 36896
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: ANGULAR RECONSTITUTION

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