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- PDB-8zym: Complex structure of 60 Fab bound to DS2 prefusion F trimer -

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Basic information

Entry
Database: PDB / ID: 8zym
TitleComplex structure of 60 Fab bound to DS2 prefusion F trimer
Components
  • Fusion glycoprotein F0,Expression tag
  • antibody light chain
  • antidody heavy chain
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Respiratory syncytial virus / prefusion F protein / DS2 / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


host cell Golgi membrane / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0
Similarity search - Domain/homology
Fusion glycoprotein F0
Similarity search - Component
Biological speciesRespiratory syncytial virus A2
synthetic construct (others)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 Å
AuthorsWang, X. / Ge, J. / Guo, F.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: NPJ Vaccines / Year: 2024
Title: DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.
Authors: Yiling Yang / Ruoke Wang / Fenglin Guo / Tian Zhao / Yuqing Lei / Qianqian Yang / Yige Zeng / Ziqing Yang / Tatchapon Ajavavarakula / Ruijie Tan / Mingxi Li / Haodi Dong / Mengyue Niu / ...Authors: Yiling Yang / Ruoke Wang / Fenglin Guo / Tian Zhao / Yuqing Lei / Qianqian Yang / Yige Zeng / Ziqing Yang / Tatchapon Ajavavarakula / Ruijie Tan / Mingxi Li / Haodi Dong / Mengyue Niu / Keyan Bao / Hao Geng / Qining Lv / Qi Zhang / Xuanling Shi / Peng Liu / Jiwan Ge / Xinquan Wang / Linqi Zhang /
Abstract: DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. ...DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2. All three vaccines elicited robust serum binding and neutralizing antibodies following intramuscular priming and boosting. DS2 induced the strongest antibody responses, followed by SC-TM and DS-Cav1. DS2 also provided strong protection against live RSV challenge. Monoclonal antibodies (mAbs) isolated from long-lived antibody-secreting cells (ASCs) in the bone marrow six months post-immunization with AdC68-DS2 predominantly targeted site Ø as well as site II. One neutralizing antibody against site II, mAb60, conferred strong protection against live RSV infection in mice. These findings highlight the strong ability of the DS2 design in eliciting long-lived antibody responses and guide the development of next-generation RSV vaccines.
History
DepositionJun 18, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Apr 30, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Fusion glycoprotein F0,Expression tag
B: Fusion glycoprotein F0,Expression tag
C: Fusion glycoprotein F0,Expression tag
D: antibody light chain
E: antibody light chain
F: antibody light chain
G: antidody heavy chain
H: antidody heavy chain
I: antidody heavy chain


Theoretical massNumber of molelcules
Total (without water)260,1489
Polymers260,1489
Non-polymers00
Water181
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Fusion glycoprotein F0,Expression tag


Mass: 61266.660 Da / Num. of mol.: 3
Mutation: S46G,E92D,V144S,A149C,S155C,S190F,V207L,S215P,S290C,L373R,Y458C,K465Q
Source method: isolated from a genetically manipulated source
Details: Sequence reference for Respiratory syncytial virus A2 (1972429) is not available in UniProt at the time of biocuration. Current sequence reference is from UniProt ID C3UPB8.
Source: (gene. exp.) Respiratory syncytial virus A2, (gene. exp.) synthetic construct (others)
Production host: Homo sapiens (human) / References: UniProt: C3UPB8
#2: Antibody antibody light chain


Mass: 12305.671 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#3: Antibody antidody heavy chain


Mass: 13143.654 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: RSV prefusion protein / Type: COMPLEX / Entity ID: #3 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Respiratory syncytial virus A2
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.21_5207: / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 82401 / Symmetry type: POINT

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