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Yorodumi- EMDB-38814: Complex of FMDV O/18074 and inter-serotype broadly neutralizing a... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38814 | |||||||||||||||||||||
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Title | Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2 | |||||||||||||||||||||
Map data | ||||||||||||||||||||||
Sample |
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Keywords | Foot-and-mouth disease virus O / Sus scrofa / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex | |||||||||||||||||||||
Function / homology | Function and homology information icosahedral viral capsid / ribonucleoside triphosphate phosphatase activity / endocytosis involved in viral entry into host cell / viral capsid / host cell cytoplasm / viral protein processing / symbiont entry into host cell / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virion attachment to host cell ...icosahedral viral capsid / ribonucleoside triphosphate phosphatase activity / endocytosis involved in viral entry into host cell / viral capsid / host cell cytoplasm / viral protein processing / symbiont entry into host cell / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virion attachment to host cell / structural molecule activity / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | Foot-and-mouth disease virus O / Sus scrofa (pig) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.44 Å | |||||||||||||||||||||
Authors | Wu S / Lei D | |||||||||||||||||||||
Funding support | China, 6 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38814.map.gz | 190.6 MB | EMDB map data format | |
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Header (meta data) | emd-38814-v30.xml emd-38814.xml | 22.2 KB 22.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_38814_fsc.xml | 17.8 KB | Display | FSC data file |
Images | emd_38814.png | 209.2 KB | ||
Masks | emd_38814_msk_1.map | 421.9 MB | Mask map | |
Filedesc metadata | emd-38814.cif.gz | 6.5 KB | ||
Others | emd_38814_half_map_1.map.gz emd_38814_half_map_2.map.gz | 391.6 MB 391.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38814 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38814 | HTTPS FTP |
-Validation report
Summary document | emd_38814_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_38814_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_38814_validation.xml.gz | 25.4 KB | Display | |
Data in CIF | emd_38814_validation.cif.gz | 33.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38814 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38814 | HTTPS FTP |
-Related structure data
Related structure data | 8y0qMC 8y0rC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_38814.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.108 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_38814_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_38814_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_38814_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of FMDV O/18074 and inter-serotype broadly neutralizing a...
Entire | Name: Complex of FMDV O/18074 and inter-serotype broadly neutralizing antibodies pOA-2 |
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Components |
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-Supramolecule #1: Complex of FMDV O/18074 and inter-serotype broadly neutralizing a...
Supramolecule | Name: 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
Supramolecule | Name: FMDV O/18074 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Foot-and-mouth disease virus O |
-Supramolecule #3: inter-serotype broadly neutralizing antibodies pOA-2
Supramolecule | Name: inter-serotype broadly neutralizing antibodies pOA-2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #5-#6 |
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Source (natural) | Organism: Sus scrofa (pig) |
-Macromolecule #1: VP1 of capsid protein
Macromolecule | Name: VP1 of capsid protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Foot-and-mouth disease virus O |
Molecular weight | Theoretical: 23.686809 KDa |
Sequence | String: 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 |
-Macromolecule #2: VP2 of capsid protein
Macromolecule | Name: VP2 of capsid protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Foot-and-mouth disease virus O |
Molecular weight | Theoretical: 24.350398 KDa |
Sequence | String: 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 |
-Macromolecule #3: VP3 of capsid protein
Macromolecule | Name: VP3 of capsid protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Foot-and-mouth disease virus O |
Molecular weight | Theoretical: 23.886848 KDa |
Sequence | String: 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 |
-Macromolecule #4: VP4 of capsid protein
Macromolecule | Name: VP4 of capsid protein / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Foot-and-mouth disease virus O |
Molecular weight | Theoretical: 8.862206 KDa |
Sequence | String: GAGQSSPTTG SQNQSGNTGS IINNYYMQQY QNSMDTQLGD NAISGGSNEG STDTTSTHTN NTQNNDWFSK LANTAFSGLF GALLA UniProtKB: Genome polyprotein |
-Macromolecule #5: pOA2 VH
Macromolecule | Name: pOA2 VH / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Sus scrofa (pig) |
Molecular weight | Theoretical: 13.721396 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EEKVVESGGG LVQPGGSLRL SCVGSGFNFK NYEINWVRQA PGKALEWLAY ITQTSDFIYY ADSVKGRFTI SRDNSRNTAY LQMNNLRTE DTARYFCTRA GLTGCKSRHC MYVWGPGAEV VVSS |
-Macromolecule #6: pOA2 VL
Macromolecule | Name: pOA2 VL / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Sus scrofa (pig) |
Molecular weight | Theoretical: 11.587944 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QTVIQEPAMS VSLGGTVTLT CGFISGSVTG TNYPSWFQQT PGQPPRLLIY YANSRPTEVP SRFSGAISGN KAALTITGAQ AEDEADYFC CLYKTNNNIL FGGGTHLTVL |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination 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 |