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- EMDB-71260: ADI-65534-bound dimer of ANDV glycoprotein tetramers -

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Basic information

Entry
Database: EMDB / ID: EMD-71260
TitleADI-65534-bound dimer of ANDV glycoprotein tetramers
Map data
Sample
  • Complex: In situ dimer of Andes virus glycoprotein tetramer bound to ADI-65534 Fab
KeywordsGn/Gc / tetramer / hantavirus / prefusion / antibody / neutralizing / quaternary epitope / VIRAL PROTEIN
Biological speciesOrthohantavirus andesense
Methodsingle particle reconstruction / cryo EM / Resolution: 6.8 Å
AuthorsMcFadden E / Guo L / McLellan JS
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U19 AI181977 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)U19 AI142777 United States
CitationJournal: bioRxiv / Year: 2025
Title: High-resolution in situ structures of hantavirus glycoprotein tetramers.
Authors: Luqiang Guo / Elizabeth McFadden / Megan M Slough / E Taylor Stone / Jacob Berrigan / Eva Mittler / Kiara Hatzakis / Troy Hinkley / Heather S Kain / Zunlong Ke / Nikole L Warner / Jesse H ...Authors: Luqiang Guo / Elizabeth McFadden / Megan M Slough / E Taylor Stone / Jacob Berrigan / Eva Mittler / Kiara Hatzakis / Troy Hinkley / Heather S Kain / Zunlong Ke / Nikole L Warner / Jesse H Erasmus / Kartik Chandran / Jason S McLellan /
Abstract: New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture ...New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture and function, however, the lack of high-resolution in situ structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly, entry, and antigenicity. Here, we leveraged a virus-like particle (VLP) system to establish a cryo-electron microscopy workflow for lattice-forming viral glycoproteins. This enabled the determination of a 2.35 Å resolution structure of the membrane-embedded Andes virus (ANDV) glycoprotein tetramer, as well as structures of dimers of tetramers and a complex with antibody ADI-65534. These structures reveal previously uncharacterized features of glycoprotein organization, stability, and pH-sensing. Immunization of mice with self-amplifying replicon RNA (repRNA) encoding ANDV-VLPs elicited high levels of glycoprotein-binding antibodies but equivalent titers of neutralizing antibodies compared to repRNA-encoded native ANDV glycoprotein complex. Collectively, these findings advance our understanding of hantavirus glycoprotein assemblies and their function, laying a foundation for structure-based vaccine design efforts.
History
DepositionJun 14, 2025-
Header (metadata) releaseJul 30, 2025-
Map releaseJul 30, 2025-
UpdateJul 30, 2025-
Current statusJul 30, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_71260.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 480 pix.
= 399.36 Å
0.83 Å/pix.
x 480 pix.
= 399.36 Å
0.83 Å/pix.
x 480 pix.
= 399.36 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density
Contour LevelBy AUTHOR: 0.05
Minimum - Maximum-0.05789965 - 0.16061346
Average (Standard dev.)0.0030134781 (±0.01345077)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 399.36002 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_71260_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_71260_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Sample components

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Entire : In situ dimer of Andes virus glycoprotein tetramer bound to ADI-6...

EntireName: In situ dimer of Andes virus glycoprotein tetramer bound to ADI-65534 Fab
Components
  • Complex: In situ dimer of Andes virus glycoprotein tetramer bound to ADI-65534 Fab

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Supramolecule #1: In situ dimer of Andes virus glycoprotein tetramer bound to ADI-6...

SupramoleculeName: In situ dimer of Andes virus glycoprotein tetramer bound to ADI-65534 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Orthohantavirus andesense

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 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: NONE
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 6.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 20080
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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