+Open data
-Basic information
Entry | Database: PDB / ID: 8kg5 | ||||||
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Title | Prefusion RSV F Bound to Lonafarnib and D25 Fab | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Respiratory syncytial virus / F protein / Lonafarnib / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information symbiont-mediated induction of syncytium formation / Translation of respiratory syncytial virus mRNAs / RSV-host interactions / Assembly and release of respiratory syncytial virus (RSV) virions / Maturation of hRSV A proteins / host cell Golgi membrane / Respiratory syncytial virus (RSV) attachment and entry / virion component / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell ...symbiont-mediated induction of syncytium formation / Translation of respiratory syncytial virus mRNAs / RSV-host interactions / Assembly and release of respiratory syncytial virus (RSV) virions / Maturation of hRSV A proteins / host cell Golgi membrane / Respiratory syncytial virus (RSV) attachment and entry / virion component / 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 / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Human respiratory syncytial virus A Enterobacteria phage T4 (virus) Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.17 Å | ||||||
Authors | Yang, Q. / Xue, B. / Liu, F. / Peng, W. / Chen, X. | ||||||
Funding support | China, 1items
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Citation | Journal: Signal Transduct Target Ther / Year: 2024 Title: Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein. Authors: Qi Yang / Bao Xue / Fengjiang Liu / Yongzhi Lu / Jielin Tang / Mengrong Yan / Qiong Wu / Ruyi Chen / Anqi Zhou / Lijie Liu / Junjun Liu / Changbin Qu / Qingxin Wu / Muqing Fu / Jiayi Zhong / ...Authors: Qi Yang / Bao Xue / Fengjiang Liu / Yongzhi Lu / Jielin Tang / Mengrong Yan / Qiong Wu / Ruyi Chen / Anqi Zhou / Lijie Liu / Junjun Liu / Changbin Qu / Qingxin Wu / Muqing Fu / Jiayi Zhong / Jianwei Dong / Sijie Chen / Fan Wang / Yuan Zhou / Jie Zheng / Wei Peng / Jinsai Shang / Xinwen Chen / Abstract: Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules ...Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8kg5.cif.gz | 288.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8kg5.ent.gz | 229.5 KB | Display | PDB format |
PDBx/mmJSON format | 8kg5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8kg5_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 8kg5_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8kg5_validation.xml.gz | 59.4 KB | Display | |
Data in CIF | 8kg5_validation.cif.gz | 84.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kg/8kg5 ftp://data.pdbj.org/pub/pdb/validation_reports/kg/8kg5 | HTTPS FTP |
-Related structure data
Related structure data | 37210MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 64530.602 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human respiratory syncytial virus A (strain A2), (gene. exp.) Enterobacteria phage T4 (virus) Gene: F, wac / Production host: Homo sapiens (human) / References: UniProt: P03420, UniProt: P10104 #2: Antibody | | Mass: 24504.629 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | | Mass: 23325.865 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Chemical | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Prefusion RSV F Bound to Lonafarnib and D25 Fab / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT | ||||||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 37059 / Symmetry type: POINT | ||||||||||||||||||||||||
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