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- EMDB-16522: Structure of ADDoCoV-ADAH11 -

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Basic information

Entry
Database: EMDB / ID: EMD-16522
TitleStructure of ADDoCoV-ADAH11
Map data
Sample
  • Complex: ADDoCoV-ADAH11
    • Complex: ADAH11
KeywordsADDomer / ADdoCov / ADAH11 / VIRUS LIKE PARTICLE
Biological speciesHuman adenovirus B3 / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.06 Å
AuthorsYadav KNS / Buzas D / Berger-Schaffitzel C / Berger I
Funding support United Kingdom, European Union, 3 items
OrganizationGrant numberCountry
Wellcome Trust210701/Z/18/Z United Kingdom
European Commission899670European Union
Wellcome Trust106115/Z/14/Z United Kingdom
CitationJournal: Antib Ther / Year: 2023
Title: generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2.
Authors: Dora Buzas / Adrian H Bunzel / Oskar Staufer / Emily J Milodowski / Grace L Edmunds / Joshua C Bufton / Beatriz V Vidana Mateo / Sathish K N Yadav / Kapil Gupta / Charlotte Fletcher / Maia K ...Authors: Dora Buzas / Adrian H Bunzel / Oskar Staufer / Emily J Milodowski / Grace L Edmunds / Joshua C Bufton / Beatriz V Vidana Mateo / Sathish K N Yadav / Kapil Gupta / Charlotte Fletcher / Maia K Williamson / Alexandra Harrison / Ufuk Borucu / Julien Capin / Ore Francis / Georgia Balchin / Sophie Hall / Mirella V Vega / Fabien Durbesson / Srikanth Lingappa / Renaud Vincentelli / Joe Roe / Linda Wooldridge / Rachel Burt / Ross J L Anderson / Adrian J Mulholland / Bristol Uncover Group / Jonathan Hare / Mick Bailey / Andrew D Davidson / Adam Finn / David Morgan / Jamie Mann / Joachim Spatz / Frederic Garzoni / Christiane Schaffitzel / Imre Berger /
Abstract: BACKGROUND: Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens.
METHODS: Here, we developed an integrated approach combining synthetic, computational and structural methods with antibody selection and immunization to design, produce and validate nature-inspired ...METHODS: Here, we developed an integrated approach combining synthetic, computational and structural methods with antibody selection and immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
RESULTS: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a ...RESULTS: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron.
CONCLUSION: Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat ...CONCLUSION: Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.
History
DepositionJan 24, 2023-
Header (metadata) releaseDec 6, 2023-
Map releaseDec 6, 2023-
UpdateDec 27, 2023-
Current statusDec 27, 2023Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_16522.png

Downloads & links

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Map

FileDownload / File: emd_16522.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.05 Å/pix.
x 480 pix.
= 504. Å		1.05 Å/pix.
x 480 pix.
= 504. Å		1.05 Å/pix.
x 480 pix.
= 504. Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.05 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.008
Minimum - Maximum-0.059325077 - 0.10001745
Average (Standard dev.)0.00046142348 (±0.0039241468)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 503.99997 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_16522_msk_1.map
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Half map: #1

Fileemd_16522_half_map_1.map
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Half map: #2

Fileemd_16522_half_map_2.map
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Sample components

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Entire : ADDoCoV-ADAH11

EntireName: ADDoCoV-ADAH11
Components
  • Complex: ADDoCoV-ADAH11
    • Complex: ADAH11

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Supramolecule #1: ADDoCoV-ADAH11

SupramoleculeName: ADDoCoV-ADAH11 / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Human adenovirus B3

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Supramolecule #2: ADAH11

SupramoleculeName: ADAH11 / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Lama glama (llama)

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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
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 55.6 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.06 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 13950
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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