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- EMDB-38814: Complex of FMDV O/18074 and inter-serotype broadly neutralizing a... -

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Basic information

Entry
Database: EMDB / ID: EMD-38814
TitleComplex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2
Map data
Sample
  • Complex: Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2
    • Complex: FMDV O/18074
      • 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
    • Complex: inter-serotype broadly neutralizing antibodies pOA-2
      • Protein or peptide: pOA2 VH
      • Protein or peptide: pOA2 VL
KeywordsFoot-and-mouth disease virus O / Sus scrofa / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex
Function / homology
Function and homology information


ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / viral capsid / host cell / host cell cytoplasm / viral protein processing / symbiont entry into host cell / cysteine-type endopeptidase activity / RNA-directed RNA polymerase activity / virion attachment to host cell ...ribonucleoside triphosphate phosphatase activity / T=pseudo3 icosahedral viral capsid / viral capsid / host cell / host cell cytoplasm / viral protein processing / symbiont entry into host cell / cysteine-type endopeptidase activity / RNA-directed RNA polymerase activity / virion attachment to host cell / structural molecule activity / membrane
Similarity search - Function
Peptidase C28, foot-and-mouth virus L-proteinase / Foot-and-mouth virus L-proteinase / Aphthovirus leader protease (L(pro)) domain profile. / Foot-and-mouth disease virus VP1 coat / Capsid protein VP4, Picornavirus / Viral protein VP4 subunit / Capsid protein VP4 superfamily, Picornavirus / Picornavirus coat protein / Papain-like cysteine peptidase superfamily / Picornavirus capsid ...Peptidase C28, foot-and-mouth virus L-proteinase / Foot-and-mouth virus L-proteinase / Aphthovirus leader protease (L(pro)) domain profile. / Foot-and-mouth disease virus VP1 coat / Capsid protein VP4, Picornavirus / Viral protein VP4 subunit / Capsid protein VP4 superfamily, Picornavirus / Picornavirus coat protein / Papain-like cysteine peptidase superfamily / Picornavirus capsid / picornavirus capsid protein / Picornavirus/Calicivirus coat protein / Viral coat protein subunit
Similarity search - Domain/homology
Genome polyprotein / Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesFoot-and-mouth disease virus O / Sus scrofa (pig)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.44 Å
AuthorsWu S / Lei D
Funding support China, 6 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32373028 China
National Natural Science Foundation of China (NSFC)32171300 China
National Natural Science Foundation of China (NSFC)32072873 China
Other government2021YFD1800304
Other governmentlzujbky-2021-ct05
Other governmentNCTIP-MY23004
CitationJournal: PLoS Pathog / Year: 2024
Title: Discovery, recognized antigenic structures, and evolution of cross-serotype broadly neutralizing antibodies from porcine B-cell repertoires against foot-and-mouth disease virus.
Authors: Fengjuan Li / Shanquan Wu / Lv Lv / Shulun Huang / Zelin Zhang / Zhaxi Zerang / Pinghua Li / Yimei Cao / Huifang Bao / Pu Sun / Xingwen Bai / Yong He / Yuanfang Fu / Hong Yuan / Xueqing Ma / ...Authors: Fengjuan Li / Shanquan Wu / Lv Lv / Shulun Huang / Zelin Zhang / Zhaxi Zerang / Pinghua Li / Yimei Cao / Huifang Bao / Pu Sun / Xingwen Bai / Yong He / Yuanfang Fu / Hong Yuan / Xueqing Ma / Zhixun Zhao / Jing Zhang / Jian Wang / Tao Wang / Dong Li / Qiang Zhang / Jijun He / Zaixin Liu / Zengjun Lu / Dongsheng Lei / Kun Li /
Abstract: It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. ...It is a great challenge to isolate the broadly neutralizing antibodies (bnAbs) against foot-and-mouth disease virus (FMDV) due to its existence as seven distinct serotypes without cross-protection. Here, by vaccination of pig with FMDV serotypes O and A whole virus antigens, we obtained 10 bnAbs against serotypes O, A and/or Asia1 by dissecting 216 common clonotypes of two serotypes O and A specific porcine B-cell receptor (BCR) gene repertoires containing total 12720 B cell clones, indicating the induction of cross-serotype bnAbs after sequential vaccination with serotypes O and A antigens. The majority of porcine bnAbs (9/10) were derived from terminally differentiated B cells of different clonal lineages, which convergently targeted the conserved "RGDL" motif on structural protein VP1 of FMDV by mimicking receptor recognition to inhibit viral attachment to cells. Cryo-EM complex structures revealed that the other bnAb pOA-2 specifically targets a novel inter-pentamer antigen structure surrounding the viral three-fold axis, with a highly conserved determinant at residue 68 on VP2. This unique binding pattern enabled cross-serotype neutralization by destabilizing the viral particle. The evolutionary analysis of pOA-2 demonstrated its origin from an intermediate B-cell, emphasizing the crucial role of somatic hypermutations (SHMs) in balancing the breadth and potency of neutralization. However, excessive SHMs may deviate from the trajectory of broad neutralization. This study provides a strategy to uncover bnAbs against highly mutable pathogens and the cross-serotype antigenic structures to explore broadly protective FMDV vaccine.
History
DepositionJan 23, 2024-
Header (metadata) releaseOct 9, 2024-
Map releaseOct 9, 2024-
UpdateNov 13, 2024-
Current statusNov 13, 2024Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_38814.png

Downloads & links

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Map

FileDownload / File: emd_38814.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.)
1.11 Å/pix.
x 480 pix.
= 531.84 Å		1.11 Å/pix.
x 480 pix.
= 531.84 Å		1.11 Å/pix.
x 480 pix.
= 531.84 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.108 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.28
Minimum - Maximum-0.06604535 - 1.7777528
Average (Standard dev.)0.0064099357 (±0.0837426)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 531.84 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_38814_msk_1.map
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Half map: #2

Fileemd_38814_half_map_1.map
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Half map: #1

Fileemd_38814_half_map_2.map
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Sample components

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Entire : Complex of FMDV O/18074 and inter-serotype broadly neutralizing a...

EntireName: Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2
Components
  • Complex: Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2
    • Complex: FMDV O/18074
      • 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
    • Complex: inter-serotype broadly neutralizing antibodies pOA-2
      • Protein or peptide: pOA2 VH
      • Protein or peptide: pOA2 VL

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Supramolecule #1: Complex of FMDV O/18074 and inter-serotype broadly neutralizing a...

SupramoleculeName: Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: FMDV O/18074

SupramoleculeName: FMDV O/18074 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#4
Source (natural)Organism: Foot-and-mouth disease virus O

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Supramolecule #3: inter-serotype broadly neutralizing antibodies pOA-2

SupramoleculeName: inter-serotype broadly neutralizing antibodies pOA-2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #5-#6
Source (natural)Organism: Sus scrofa (pig)

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Macromolecule #1: VP1 of capsid protein

MacromoleculeName: VP1 of capsid protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus O
Molecular weightTheoretical: 23.686809 KDa
SequenceString: TTSAGESADP VTTTVENYGG ETQAQRRQHT DVTFILDRFV KVKPQEEINV LDLMQIPAHT LVGALLRTAT YYFSDLELAV KHEGDLTWV PNGAPEAALD NTTNPTAYHK EPLTRLALPY TAPHRVLATV YNGSNKYGDT STNNVRGDLH VLAKNAERTL P TSFNYGAI ...String:
TTSAGESADP VTTTVENYGG ETQAQRRQHT DVTFILDRFV KVKPQEEINV LDLMQIPAHT LVGALLRTAT YYFSDLELAV KHEGDLTWV PNGAPEAALD NTTNPTAYHK EPLTRLALPY TAPHRVLATV YNGSNKYGDT STNNVRGDLH VLAKNAERTL P TSFNYGAI KATRVTELLY RMKRAETYCP RPLLAIQPST ARHKQKIVAP VKQLL

UniProtKB: Genome polyprotein

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Macromolecule #2: VP2 of capsid protein

MacromoleculeName: VP2 of capsid protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus O
Molecular weightTheoretical: 24.350398 KDa
SequenceString: DKKTEETTLL EDRILTTRNG HTTSTTQSSV GVTYGYATAE DFVSGPNTSG LETRVVQAER FFKTHLFDWG TNDSFGRCHL LELPTDHKG VYGSLTDSYA YMRNGWDVEV TAVGNQFNGG CLLVAMVPEL CSITKRELYQ LTLFPHQFIN PRTNMTAHIT V PYLGVNRY ...String:
DKKTEETTLL EDRILTTRNG HTTSTTQSSV GVTYGYATAE DFVSGPNTSG LETRVVQAER FFKTHLFDWG TNDSFGRCHL LELPTDHKG VYGSLTDSYA YMRNGWDVEV TAVGNQFNGG CLLVAMVPEL CSITKRELYQ LTLFPHQFIN PRTNMTAHIT V PYLGVNRY DQYKVHKPWT LVVTVVAPLT VKNEGAPQIK VYANIAPTNV YVAGELPSKE

UniProtKB: Genome polyprotein

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Macromolecule #3: VP3 of capsid protein

MacromoleculeName: VP3 of capsid protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus O
Molecular weightTheoretical: 23.886848 KDa
SequenceString: GIFPVACSDG YGGLVTTDPK TADPVYGKVF NPPRNLLPGR FTNLLDVAEA CPTFLRFDSD VPYVTTKTDS DRKLVQFDLS LAAKHMSNT FLAGLAQYYT QYSGTINLHF MFTGPTDAKA RYMVAYAPPG MEPPTTPEAA AHCIHAEWDT GLNSKFTFSI P YLSAADYA ...String:
GIFPVACSDG YGGLVTTDPK TADPVYGKVF NPPRNLLPGR FTNLLDVAEA CPTFLRFDSD VPYVTTKTDS DRKLVQFDLS LAAKHMSNT FLAGLAQYYT QYSGTINLHF MFTGPTDAKA RYMVAYAPPG MEPPTTPEAA AHCIHAEWDT GLNSKFTFSI P YLSAADYA YTASDVAETT NVQGWVCLFQ ITHGKADGDA LVVLASAGKD FDLRLPVDAR AQ

UniProtKB: Genome polyprotein

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Macromolecule #4: VP4 of capsid protein

MacromoleculeName: VP4 of capsid protein / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Foot-and-mouth disease virus O
Molecular weightTheoretical: 8.862206 KDa
SequenceString:
GAGQSSPTTG SQNQSGNTGS IINNYYMQQY QNSMDTQLGD NAISGGSNEG STDTTSTHTN NTQNNDWFSK LANTAFSGLF GALLA

UniProtKB: Genome polyprotein

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Macromolecule #5: pOA2 VH

MacromoleculeName: pOA2 VH / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Sus scrofa (pig)
Molecular weightTheoretical: 13.721396 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EEKVVESGGG LVQPGGSLRL SCVGSGFNFK NYEINWVRQA PGKALEWLAY ITQTSDFIYY ADSVKGRFTI SRDNSRNTAY LQMNNLRTE DTARYFCTRA GLTGCKSRHC MYVWGPGAEV VVSS

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Macromolecule #6: pOA2 VL

MacromoleculeName: pOA2 VL / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Sus scrofa (pig)
Molecular weightTheoretical: 11.587944 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QTVIQEPAMS VSLGGTVTLT CGFISGSVTG TNYPSWFQQT PGQPPRLLIY YANSRPTEVP SRFSGAISGN KAALTITGAQ AEDEADYFC CLYKTNNNIL FGGGTHLTVL

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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: 7.2
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k 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: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 2.44 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 3202
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3)
FSC plot (resolution estimation)

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