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- EMDB-71803: HDV particle subtomogram reconstruction -

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Basic information

Entry
Database: EMDB / ID: EMD-71803
TitleHDV particle subtomogram reconstruction
Map dataHDV particle subtomogram reconstruction. Unsharpened.
Sample
  • Virus: Hepatitis delta virus
KeywordsHDV / HDAg / RNP / cryo-ET / VIRUS
Biological speciesHepatitis delta virus
Methodsubtomogram averaging / cryo EM / Resolution: 36.0 Å
AuthorsItskanov S / Lansdon EB
Funding support United States, 1 items
OrganizationGrant numberCountry
Not funded United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: Structural characterization of the HDV virion and its ribonucleoprotein.
Authors: Samuel Itskanov / Beatrice Ary / Upasana Mehra / Irene Lew / Nikolai Novikov / Uli Schmitz / Meghan M Holdorf / Rudolf K Beran / Eric B Lansdon /
Abstract: Hepatitis D virus (HDV) is a small RNA satellite virus of hepatitis B virus (HBV) which encodes a single protein, HDV delta antigen (HDAg), that is required for replication. Viral replication occurs ...Hepatitis D virus (HDV) is a small RNA satellite virus of hepatitis B virus (HBV) which encodes a single protein, HDV delta antigen (HDAg), that is required for replication. Viral replication occurs independently from HBV and relies primarily on host RNA polymerase(s). Bulevirtide, a viral entry inhibitor, is the only approved treatment for chronic HDV but has a low cure rate as a monotherapy, and most patients rebound following cessation of therapy. It is likely that an inhibitor targeting HDV replication is necessary to achieve HDV cure, but the paucity of HDV-derived elements and limited understanding of HDV replication presents a significant therapeutic challenge. Understanding the precise mechanism of interactions between HDAg and viral RNA, and how it is packaged within the virion can inspire structure-guided drug design targeting replication. Using cryoelectron tomography and single particle cryoelectron microscopy, we present reconstructions of the virion and viral RNPs. We observed multiple binding configurations in vitro that suggest a propensity to arrange four RNA segments around repeating units of HDAg in a ladder-like formation. The oligomerization domains of a homo-octameric HDAg complex are directly involved in RNA binding by utilizing the vertices and sides of its square-shaped architecture to bind RNA in a sequence-promiscuous fashion. Structure-function analysis reveals that these RNA contact sites are important for viral replication and their disruption may be a potential avenue for next-generation antivirals to treat HDV.
History
DepositionJul 23, 2025-
Header (metadata) releaseJan 28, 2026-
Map releaseJan 28, 2026-
UpdateApr 1, 2026-
Current statusApr 1, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71803.png

Downloads & links

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Map

FileDownload / File: emd_71803.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationHDV particle subtomogram reconstruction. Unsharpened.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 512 pix.
= 474.624 Å		0.93 Å/pix.
x 512 pix.
= 474.624 Å		0.93 Å/pix.
x 512 pix.
= 474.624 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.927 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.81
Minimum - Maximum-9.663264 - 8.652202000000001
Average (Standard dev.)0.11088438 (±0.99997455)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin276276276
Dimensions512512512
Spacing512512512
CellA=B=C: 474.624 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: HDV particle subtomogram reconstruction. Half map - even.

Fileemd_71803_half_map_1.map
AnnotationHDV particle subtomogram reconstruction. Half map - even.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: HDV particle subtomogram reconstruction. Half map - odd.

Fileemd_71803_half_map_2.map
AnnotationHDV particle subtomogram reconstruction. Half map - odd.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Hepatitis delta virus

EntireName: Hepatitis delta virus
Components
  • Virus: Hepatitis delta virus

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Supramolecule #1: Hepatitis delta virus

SupramoleculeName: Hepatitis delta virus / type: virus / ID: 1 / Parent: 0 / NCBI-ID: 12475 / Sci species name: Hepatitis delta virus / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No
Host (natural)Organism: Homo sapiens (human)
Virus shellShell ID: 1 / Diameter: 350.0 Å

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Experimental details

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Structure determination

Methodcryo EM
Processingsubtomogram averaging
Aggregation stateparticle

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Sample preparation

BufferpH: 8 / Details: 25mM Tris-HCl pH 8.0, 150mM NaCl, 1mM EDTA
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 10 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 1.6 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 4.0 µm / Nominal defocus min: 1.5 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 36.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: EMAN2 / Number subtomograms used: 358
ExtractionNumber tomograms: 912 / Number images used: 358 / Software - Name: EMAN2
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Final 3D classificationNumber classes: 1
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: EMAN2
FSC plot (resolution estimation)

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