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- EMDB-73671: Structure of SS-L2-LuSNP -

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Basic information

Entry
Database: EMDB / ID: EMD-73671
TitleStructure of SS-L2-LuSNP
Map dataCryo-EM map
Sample
  • Complex: Structure of SS-L2-LuSNP
KeywordsProtein Nanoparticles Vaccines / VIRUS LIKE PARTICLE
Biological speciesMammalian expression vector Flag-MCS-pcDNA3.1 (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.22 Å
AuthorsDzuvor CK / Corbett-Helaire KS
Funding support United States, 1 items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: bioRxiv / Year: 2025
Title: Unconventional linkers facilitate potent stabilized coronavirus stem antibody responses following nanoparticle vaccination.
Authors: Christian K O Dzuvor / Sydney P Moak / Lindsay R McManus / Abigail E Dzordzorme / Lamount R Evanson / Taewoo Kim / Abigail Thomas / Olayimika Adeyemi / Valerie Foley / Aditi Limaye / Ryan P ...Authors: Christian K O Dzuvor / Sydney P Moak / Lindsay R McManus / Abigail E Dzordzorme / Lamount R Evanson / Taewoo Kim / Abigail Thomas / Olayimika Adeyemi / Valerie Foley / Aditi Limaye / Ryan P McNamara / Kizzmekia S Corbett-Helaire /
Abstract: Vaccine technologies that protect against a range of related pathogens within viral families, such as human immunodeficiency virus (HIV), influenza, and coronaviruses (CoVs) represent the future of ...Vaccine technologies that protect against a range of related pathogens within viral families, such as human immunodeficiency virus (HIV), influenza, and coronaviruses (CoVs) represent the future of viral vaccine development. Towards developing broad-spectrum CoV and influenza vaccines, we and others previously designed and evaluated CoV and influenza stem antigens; but these elicited relatively weak and sub-neutralizing antibody (Ab) responses. Multivalent antigen display on nanoparticles (NPs) is an established strategy to enhance and shape immunogenicity. However, one facet of NP vaccines has been largely overlooked: the indispensable linker segment between the antigen and NP core. Here, we introduce -designed rigid (L2) and rarely used long flexible (L6) linkers to optimally display antigens on NPs, target occluded epitopes, and enhance cross-reactive Ab responses, using prefusion-stabilized Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S-2P) and stem (SS) antigens as prototype antigens. Antigenic characterization of L2-NPs confirmed enhanced Ab binding and exposure of cross-reactive epitopes compared with L6-NPs and soluble antigens. Immunization with SS-L2-NPs elicited broader, more potent cross-reactive Ab responses across the seven human-infecting CoVs and pandemic threat WIV1-CoV, whereas SS-L6-NPs induced stronger neutralizing Ab responses against MERS-CoV, SARS-CoV-2, and WIV1-CoV. Ab competition and systems serology analyses revealed that SS-L2-NPs elicit robust Fc-mediated effector functions. By improving CoV-targeting Ab functionality, these linker approaches have the potential to confer broad-spectrum CoV protection and represent a promising strategy against hypervariable influenza and HIV viruses - as well as other broad viral families with pandemic potential.
History
DepositionOct 30, 2025-
Header (metadata) releaseOct 7, 2026-
Map releaseOct 7, 2026-
UpdateOct 7, 2026-
Current statusOct 7, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_73671.png

Downloads & links

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Map

FileDownload / File: emd_73671.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 440 pix.
= 484. Å		1.1 Å/pix.
x 440 pix.
= 484. Å		1.1 Å/pix.
x 440 pix.
= 484. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.125
Minimum - Maximum-0.20516336 - 0.494314
Average (Standard dev.)0.00039768088 (±0.028636169)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 484.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_73671_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Cryo-EM map half A

Fileemd_73671_half_map_1.map
AnnotationCryo-EM map half A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Cryo-EM map half

Fileemd_73671_half_map_2.map
AnnotationCryo-EM map half
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Structure of SS-L2-LuSNP

EntireName: Structure of SS-L2-LuSNP
Components
  • Complex: Structure of SS-L2-LuSNP

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Supramolecule #1: Structure of SS-L2-LuSNP

SupramoleculeName: Structure of SS-L2-LuSNP / type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Mammalian expression vector Flag-MCS-pcDNA3.1 (others)

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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 TALOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.57 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm

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Image processing

CTF correctionType: NONE
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.22 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 24359
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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