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- EMDB-45773: JN.1 spike/Nanosota-9 complex -

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Basic information

Entry
Database: EMDB / ID: EMD-45773
TitleJN.1 spike/Nanosota-9 complex
Map dataunsharpened map of JN.1 spike/Nanosota-9 complex
Sample
  • Complex: JN.1 spike/Nanosota-9 complex
    • Complex: JN.1 spike
      • Protein or peptide: Spike glycoprotein
    • Complex: Nanosota-9
      • Protein or peptide: Nanosota-9
KeywordsEBOV glycoprotein / nanobody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / symbiont-mediated-mediated suppression of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / host cell surface receptor binding / symbiont-mediated suppression of host innate immune response / endocytosis involved in viral entry into host cell / receptor ligand activity / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane
Similarity search - Function
Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus ...Spike (S) protein S1 subunit, receptor-binding domain, SARS-CoV-2 / Spike (S) protein S1 subunit, N-terminal domain, SARS-CoV-like / Coronavirus spike glycoprotein S1, C-terminal / Coronavirus spike glycoprotein S1, C-terminal / Spike glycoprotein, betacoronavirus / Spike glycoprotein, N-terminal domain superfamily / Betacoronavirus spike (S) glycoprotein S1 subunit N-terminal (NTD) domain profile. / Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile. / Spike (S) protein S1 subunit, receptor-binding domain, betacoronavirus / Spike S1 subunit, receptor binding domain superfamily, betacoronavirus / Betacoronavirus spike glycoprotein S1, receptor binding / Spike glycoprotein S1, N-terminal domain, betacoronavirus-like / Betacoronavirus-like spike glycoprotein S1, N-terminal / Spike glycoprotein S2, coronavirus, heptad repeat 1 / Spike glycoprotein S2, coronavirus, heptad repeat 2 / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 1 (HR1) region profile. / Coronavirus spike (S) glycoprotein S2 subunit heptad repeat 2 (HR2) region profile. / Spike glycoprotein S2 superfamily, coronavirus / Spike glycoprotein S2, coronavirus / Coronavirus spike glycoprotein S2
Similarity search - Domain/homology
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.99 Å
AuthorsYe G / Bu F / Liu B / Li F
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI089728 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI110700 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI171954 United States
CitationJournal: PLoS Pathog / Year: 2024
Title: Discovery of Nanosota-9 as anti-Omicron nanobody therapeutic candidate.
Authors: Gang Ye / Fan Bu / Divyasha Saxena / Hailey Turner-Hubbard / Morgan Herbst / Benjamin Spiller / Brian E Wadzinski / Lanying Du / Bin Liu / Jian Zheng / Fang Li /
Abstract: Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic ...Omicron subvariants of SARS-CoV-2 continue to pose a significant global health threat. Nanobodies, single-domain antibodies derived from camelids, are promising therapeutic tools against pandemic viruses due to their favorable properties. In this study, we identified a novel nanobody, Nanosota-9, which demonstrates high potency against a wide range of Omicron subvariants both in vitro and in a mouse model. Cryo-EM data revealed that Nanosota-9 neutralizes Omicron through a unique mechanism: two Nanosota-9 molecules crosslink two receptor-binding domains (RBDs) of the trimeric Omicron spike protein, preventing the RBDs from binding to the ACE2 receptor. This mechanism explains its strong anti-Omicron potency. Additionally, the Nanosota-9 binding epitopes on the spike protein are relatively conserved among Omicron subvariants, contributing to its broad anti-Omicron spectrum. Combined with our recently developed structure-guided in vitro evolution approach for nanobodies, Nanosota-9 has the potential to serve as the foundation for a superior anti-Omicron therapeutic.
History
DepositionJul 16, 2024-
Header (metadata) releaseNov 20, 2024-
Map releaseNov 20, 2024-
UpdateDec 11, 2024-
Current statusDec 11, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_45773.png

Downloads & links

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Map

FileDownload / File: emd_45773.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationunsharpened map of JN.1 spike/Nanosota-9 complex
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.89 Å/pix.
x 384 pix.
= 339.968 Å		0.89 Å/pix.
x 384 pix.
= 339.968 Å		0.89 Å/pix.
x 384 pix.
= 339.968 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.88533 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0517
Minimum - Maximum-0.29838568 - 0.7123113
Average (Standard dev.)0.00018867679 (±0.0169767)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 339.968 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: sharpened map of JN.1 spike/Nanosota-9 complex

Fileemd_45773_additional_1.map
Annotationsharpened map of JN.1 spike/Nanosota-9 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A of JN.1 spike/Nanosota-9 complex

Fileemd_45773_half_map_1.map
Annotationhalf map_A of JN.1 spike/Nanosota-9 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B of JN.1 spike/Nanosota-9 complex

Fileemd_45773_half_map_2.map
Annotationhalf map_B of JN.1 spike/Nanosota-9 complex
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : JN.1 spike/Nanosota-9 complex

EntireName: JN.1 spike/Nanosota-9 complex
Components
  • Complex: JN.1 spike/Nanosota-9 complex
    • Complex: JN.1 spike
      • Protein or peptide: Spike glycoprotein
    • Complex: Nanosota-9
      • Protein or peptide: Nanosota-9

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Supramolecule #1: JN.1 spike/Nanosota-9 complex

SupramoleculeName: JN.1 spike/Nanosota-9 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: JN.1 spike

SupramoleculeName: JN.1 spike / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 / Details: Recombinant spike protein
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2

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Supramolecule #3: Nanosota-9

SupramoleculeName: Nanosota-9 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 / Details: recombinant nanobody
Source (natural)Organism: Vicugna pacos (alpaca)

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Macromolecule #1: Spike glycoprotein

MacromoleculeName: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Details: JN.1 spike / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Molecular weightTheoretical: 139.255891 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDAMKRGLCC VLLLCGAVFV SASQCVMPLF NLITTTQSYT NSFTRGVYYP DKVFRSSVLH LTQDLFLPFF SNVTWFHAIS GTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVFIKV CEFQFCNDPF LDVYHKNNKS W MESESGVY ...String:
MDAMKRGLCC VLLLCGAVFV SASQCVMPLF NLITTTQSYT NSFTRGVYYP DKVFRSSVLH LTQDLFLPFF SNVTWFHAIS GTNGTKRFD NPVLPFNDGV YFASTEKSNI IRGWIFGTTL DSKTQSLLIV NNATNVFIKV CEFQFCNDPF LDVYHKNNKS W MESESGVY SSANNCTFEY VSQPFLMDLE GKQGNFKNLR EFVFKNIDGY FKIYSKHTPI IGRDFPQGFS ALEPLVDLPI GI NITRFQT LLALNRSYLT PGDSSSGWTA GAADYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIY QTSNFR VQPTESIVRF PNVTNLCPFH EVFNATRFAS VYAWNRTRIS NCVADYSVLY NFAPFFAFKC YGVSPTKLND LCFT NVYAD SFVIKGNEVS QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKHSGN YDYWYRSFRK SKLKPFERDI STEIY QAGN KPCKGKGPNC YFPLQSYGFR PTYGVGHQPY RVVVLSFELL HAPATVCGPK KSTNLVKNKC VNFNFNGLTG TGVLTK SNK KFLPFQQFGR DIVDTTDAVR DPQTLEILDI TPCSFGGVSV ITPGTNTSNQ VAVLYQGVNC TEVSVAIHAD QLTPTWR VY STGSNVFQTR AGCLIGAEYV NNSYECDIPI GAGICASYQT QTKSRAGARS VASQSIIAYT MSLGAENSVA YSNNSIAI P TNFTISVTTE ILPVSMTKTS VDCTMYICGD STECSNLLLQ YGSFCTQLKR ALTGIAVEQD KNTQEVFAQV KQIYKTPPI KYFGGFNFSQ ILPDPSKPSK RSPIEDLLFN KVTLADAGFI KQYGDCLGDI AARDLICAQK FNGLTVLPPL LTDEMIAQYT SALLAGTIT SGWTFGAGPA LQIPFPMQMA YRFNGIGVTQ NVLYENQKLI ANQFNSAIGK IQDSLFSTPS ALGKLQDVVN H NAQALNTL VKQLSSKFGA ISSVLNDILS RLDPPEAEVQ IDRLITGRLQ SLQTYVTQQL IRAAEIRASA NLAATKMSEC VL GQSKRVD FCGKGYHLMS FPQSAPHGVV FLHVTYVPAQ EKNFTTAPAI CHDGKAHFPR EGVFVSNGTH WFVTQRNFYE PQI ITTDNT FVSGNCDVVI GIVNNTVYDP LQLELDSFKE ELDKYFKNHT SPDVDLGDIS GINASVVNIQ KEIDRLNEVA KNLN ESLID LQELGKYEQY IKGSGYIPEA PRDGQAYVRK DGEWVLLSTF LGHHHHHH

UniProtKB: Spike glycoprotein

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Macromolecule #2: Nanosota-9

MacromoleculeName: Nanosota-9 / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 16.311601 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLQESGGG LVQPGGSLRL SCTASGIALH THATGWFRQA PGKEREGVSC ISSGDGTTYY EDSVEGRFTI SRDNAKNTVY LQMNSLKLE DTAVYYCAAD PGAVCHSGSY YYTDDDFYYR GQGTQVTVSS GGQHHHHHHG AYPYDVPDYA S

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 54.8 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: 1.1 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.99 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 248315
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

8ios


Chain - Source name: PDB / Chain - Initial model type: experimental model
Output model

PDB-9co8:
JN.1 spike/Nanosota-9 complex

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