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- PDB-7eo0: FOOT AND MOUTH DISEASE VIRUS O/TIBET/99-BOUND THE SINGLE CHAIN FR... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7eo0 | ||||||
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Title | FOOT AND MOUTH DISEASE VIRUS O/TIBET/99-BOUND THE SINGLE CHAIN FRAGMEN ANTIBODY C4 | ||||||
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Function / homology | ![]() Immunoglobulin V-Type / ![]() ![]() ![]() Similarity search - Domain/homology | ||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | He, Y. / Li, K. | ||||||
![]() | ![]() Title: Two Cross-Protective Antigen Sites on Foot-and-Mouth Disease Virus Serotype O Structurally Revealed by Broadly Neutralizing Antibodies from Cattle. Authors: Kun Li / Yong He / Li Wang / Pinghua Li / Sheng Wang / Pu Sun / Huifang Bao / Yimei Cao / Xuerong Liu / Guoqiang Zhu / Yali Song / Xingwen Bai / Xueqing Ma / Yuanfang Fu / Hong Yuan / Jing ...Authors: Kun Li / Yong He / Li Wang / Pinghua Li / Sheng Wang / Pu Sun / Huifang Bao / Yimei Cao / Xuerong Liu / Guoqiang Zhu / Yali Song / Xingwen Bai / Xueqing Ma / Yuanfang Fu / Hong Yuan / Jing Zhang / Jian Wang / Yingli Chen / Dong Li / Zhiyong Lou / Zaixin Liu / Zengjun Lu / ![]() Abstract: Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen ...Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen sites that induce neutralizing antibodies have been defined, studies on cross-protective antigen sites are still scarce. We mapped two cross-protective antigen sites using 13 bovine-derived broadly neutralizing monoclonal antibodies (bnAbs) capable of neutralizing 4 lineages within 3 topotypes of FMDV serotype O. One antigen site was formed by a novel cluster of VP3-focused epitopes recognized by bnAb C4 and C4-like antibodies. The cryo-electron microscopy (cryo-EM) structure of the FMDV-OTi (O/Tibet/99)-C4 complex showed close contact with VP3 and a novel interprotomer antigen epitope around the icosahedral 3-fold axis of the FMDV particle, which is far beyond the known antigen site 4. The key determinants of the neutralizing function of C4 and C4-like antibodies on the capsid were βB (T65), the B-C loop (T68), the E-F loop (E131 and K134), and the H-I loop (G196), revealing a novel antigen site on VP3. The other antigen site comprised two group epitopes on VP2 recognized by 9 bnAbs (B57, B73, B77, B82, F28, F145, F150, E46, and E54), which belong to the known antigen site 2 of FMDV serotype O. Notably, bnAb C4 potently promoted FMDV RNA release in response to damage to viral particles, suggesting that the targeted epitope contains a trigger mechanism for particle disassembly. This study revealed two cross-protective antigen sites that can elicit cross-reactive neutralizing antibodies in cattle and provided new structural information for the design of a broad-spectrum molecular vaccine against FMDV serotype O. FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response. Monoclonal neutralization antibodies provide both crucial defense components against FMDV infection and valuable tools for fine analysis of the antigenic structure. In this study, we found a cluster of novel VP3-focused epitopes using 13 bnAbs against FMDV serotype O from natural host cattle, which revealed two cross-protective antigen sites on VP2 and VP3. Antibody C4 targeting this novel epitope potently promoted viral particle disassembly and RNA release before infection, which may indicate a vulnerable region of FMDV. This study reveals new structural information about cross-protective antigen sites of FMDV serotype O, providing valuable and strong support for future research on broad-spectrum vaccines against FMD. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 164.1 KB | Display | ![]() |
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PDB format | ![]() | 131.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 31223MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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3 | ![]()
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4 | ![]()
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5 | ![]()
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Symmetry | Point symmetry: (Schoenflies symbol![]() ![]() |
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Components
-Protein , 5 types, 5 molecules 1234H
#1: Protein | Mass: 23524.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
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#2: Protein | Mass: 24338.387 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#3: Protein | Mass: 23875.801 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#4: Protein | Mass: 8778.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() |
#5: Protein | Mass: 13914.535 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
-Antibody , 1 types, 1 molecules L
#6: Antibody | Mass: 12794.880 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Source (natural) |
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Source (recombinant) | Organism: ![]() ![]() ![]() | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||
Vitrification![]() | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: OTHER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
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Processing
CTF correction![]() | Type: NONE |
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3D reconstruction![]() | Resolution: 3.75 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 14458 / Symmetry type: POINT |
Refinement | Highest resolution: 3.75 Å |