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- EMDB-34637: cocktail of FMDV (A/TUR/14/98) in complex with M678F and M688F -

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Basic information

Entry
Database: EMDB / ID: EMD-34637
Titlecocktail of FMDV (A/TUR/14/98) in complex with M678F and M688F
Map data
Sample
  • Complex: FMDV capsid protein in complex with M678F nab and M688F nab
    • Protein or peptide: M678F nab
    • Protein or peptide: M688F nab
    • Protein or peptide: VP1 of capsid protein
    • Protein or peptide: VP2 of capsid protein
    • Protein or peptide: VP3 of capsid protein
    • Protein or peptide: VP4 of capsid protein
KeywordsFMDV / antibody / VIRUS
Function / homology
Function and homology information


icosahedral viral capsid / host cell cytoplasm / symbiont entry into host cell / virion attachment to host cell / structural molecule activity / cytoplasm
Similarity search - Function
Foot-and-mouth disease virus VP1 coat / Capsid protein VP4, Picornavirus / Viral protein VP4 subunit / Capsid protein VP4 superfamily, Picornavirus / Picornavirus coat protein / Picornavirus capsid / picornavirus capsid protein / Picornavirus/Calicivirus coat protein / Viral coat protein subunit
Similarity search - Domain/homology
Biological speciesFoot-and-mouth disease virus A / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsLi HZ / Dong H / Liu P
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2024
Title: Foot-and-mouth disease virus antigenic landscape and reduced immunogenicity elucidated in atomic detail.
Authors: Haozhou Li / Pan Liu / Hu Dong / Aldo Dekker / Michiel M Harmsen / Huichen Guo / Xiangxi Wang / Shiqi Sun /
Abstract: Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a ...Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a mechanism that remains elusive. Here, we present the high-resolution structures of 12S (3.2 Å) and its immune complex of a single-domain antibody (VHH) targeting the particle interior (3.2 Å), as well as two 146S-specific VHHs complexed to distinct sites on the 146S capsid surface (3.6 Å and 2.9 Å). The antigenic landscape of 146S is depicted using 13 known FMD virus-antibody complexes. Comparison of the immunogenicity of 146S and 12S in pigs, focusing on the resulting antigenic sites and incorporating structural analysis, reveals that dissociation of 146S leads to structural alteration and destruction of multiple epitopes, resulting in significant differences in antibody profiles/lineages induced by 12S and 146S. Furthermore, 146S generates higher synergistic neutralizing antibody titers compared to 12S, whereas both particles induce similar total FMD virus specific antibody titers. This study can guide the structure-based rational design of novel multivalent and broad-spectrum recombinant vaccines for protection against FMD.
History
DepositionOct 28, 2022-
Header (metadata) releaseNov 1, 2023-
Map releaseNov 1, 2023-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_34637.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.36 Å/pix.
x 360 pix.
= 489.6 Å
1.36 Å/pix.
x 360 pix.
= 489.6 Å
1.36 Å/pix.
x 360 pix.
= 489.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.36 Å
Density
Contour LevelBy AUTHOR: 0.06
Minimum - Maximum-0.27311864 - 0.4062032
Average (Standard dev.)0.0018469774 (±0.023299439)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 489.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_34637_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_34637_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : FMDV capsid protein in complex with M678F nab and M688F nab

EntireName: FMDV capsid protein in complex with M678F nab and M688F nab
Components
  • Complex: FMDV capsid protein in complex with M678F nab and M688F nab
    • Protein or peptide: M678F nab
    • Protein or peptide: M688F nab
    • Protein or peptide: VP1 of capsid protein
    • Protein or peptide: VP2 of capsid protein
    • Protein or peptide: VP3 of capsid protein
    • Protein or peptide: VP4 of capsid protein

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Supramolecule #1: FMDV capsid protein in complex with M678F nab and M688F nab

SupramoleculeName: FMDV capsid protein in complex with M678F nab and M688F nab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Foot-and-mouth disease virus A

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Macromolecule #1: M678F nab

MacromoleculeName: M678F nab / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 12.753181 KDa
Recombinant expressionOrganism: Yeast centromeric expression vector p416GPD (others)
SequenceString:
QVQLQESGGG LVQAGGSLRL SCVYSGGAYS MGWYRQAPGK QRELVAAITD DGITNYRDTV KGRFTISRDN AKKAVYLQMN SLKPEDTAV YHCNTVRRVA TLSGSSSGSW GQGTQVTVSS

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Macromolecule #2: M688F nab

MacromoleculeName: M688F nab / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 13.861437 KDa
Recombinant expressionOrganism: Yeast centromeric expression vector p416GPD (others)
SequenceString:
QVQLQESGGG LVQAGDSLRL SCVPSVRTSD NYIMGWFRQP PGKEREFVAA IRRSDGTTKY AASVKGRFAI SRDVAKNAAY LQMNSLKAE DTAVYYCAAK YQSTFYSTMD VQYDYWGQGT QVTVSS

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Macromolecule #3: VP1 of capsid protein

MacromoleculeName: VP1 of capsid protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus A
Molecular weightTheoretical: 23.111094 KDa
SequenceString: TTSAGESADP VTTTVENYGG ETQVQRRHHT DVGFIMDRFV KINNTNPTHV IDLMQTHQHG LVGALLRAAT YYFSDLEIVV RHEGNLTWV PNGAPEAALS NAGNPTAYNK APFTRLALPY TAPHRVLATV YNGTSKYSTT GERTRGDLGA LAARVATQLP A SFNFGAIR ...String:
TTSAGESADP VTTTVENYGG ETQVQRRHHT DVGFIMDRFV KINNTNPTHV IDLMQTHQHG LVGALLRAAT YYFSDLEIVV RHEGNLTWV PNGAPEAALS NAGNPTAYNK APFTRLALPY TAPHRVLATV YNGTSKYSTT GERTRGDLGA LAARVATQLP A SFNFGAIR ATDISELLVR MKRAELYCPR PLLAVEVTAQ DRHKQKIIAP AKQ

UniProtKB: Genome polyprotein

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Macromolecule #4: VP2 of capsid protein

MacromoleculeName: VP2 of capsid protein / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus A
Molecular weightTheoretical: 24.575779 KDa
SequenceString: DKKTEETTLL EDRTLTTRNG HTTSTTQSSV GVTYGYSTGE DHVSGPNTSG LETRVTQAER FFKKHLFNWT TDKPFGHLEK LKLPTDHKG VYGHLVDSFA YMRNGWDVEV SAVGNQFNGG CLLVAMVPEW KKFTPREKYQ LTLFPHQFIS PRTNMTAHIT V PYLGVNRY ...String:
DKKTEETTLL EDRTLTTRNG HTTSTTQSSV GVTYGYSTGE DHVSGPNTSG LETRVTQAER FFKKHLFNWT TDKPFGHLEK LKLPTDHKG VYGHLVDSFA YMRNGWDVEV SAVGNQFNGG CLLVAMVPEW KKFTPREKYQ LTLFPHQFIS PRTNMTAHIT V PYLGVNRY DQYKKHKPWT LVVMVVSPLT TSSIGATEIK VYANIAPTHV HVAGELPSKE

UniProtKB: Genome polyprotein

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Macromolecule #5: VP3 of capsid protein

MacromoleculeName: VP3 of capsid protein / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus A
Molecular weightTheoretical: 24.284121 KDa
SequenceString: GIVPVACSDG YGGLVTTDPK TADPVYGKVY NPPRTNYPGR FTNLLDVAEA CPTFLCFDDG KPYVVTREDE QRLLAKFDVS LAAKHMSNT YLSGIAQYYA QYSGTINLHF MFTGSTDSKA RYMVAYVPPG VETPPDTPER AAHCIHAEWD TGLNSKFTFS I PYVSAADY ...String:
GIVPVACSDG YGGLVTTDPK TADPVYGKVY NPPRTNYPGR FTNLLDVAEA CPTFLCFDDG KPYVVTREDE QRLLAKFDVS LAAKHMSNT YLSGIAQYYA QYSGTINLHF MFTGSTDSKA RYMVAYVPPG VETPPDTPER AAHCIHAEWD TGLNSKFTFS I PYVSAADY AYTASDVAET TNVQGWVCIY QITHGKAQND TLVVSVSAGK DFELRLPIDP RTQ

UniProtKB: Genome polyprotein

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Macromolecule #6: VP4 of capsid protein

MacromoleculeName: VP4 of capsid protein / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus A
Molecular weightTheoretical: 8.778129 KDa
SequenceString:
GAGQSSPATG SQNQSGNTGS IINNYYMQQY QNSMDTQLGD NAISGGSNEG STDTTSTHTT NTQNNDWFSK LASSAFSGLF GALLA

UniProtKB: Genome polyprotein

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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
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 30.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.2 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: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 34373
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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