+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37210 | |||||||||
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Title | Prefusion RSV F Bound to Lonafarnib and D25 Fab | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Respiratory syncytial virus / F protein / Lonafarnib / VIRAL PROTEIN/IMMUNE SYSTEM / 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 (strain A2) / Enterobacteria phage T4 (virus) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.17 Å | |||||||||
Authors | Yang Q / Xue B / Liu F / Peng W / Chen X | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37210.map.gz | 204 MB | EMDB map data format | |
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Header (meta data) | emd-37210-v30.xml emd-37210.xml | 17.3 KB 17.3 KB | Display Display | EMDB header |
Images | emd_37210.png | 20.2 KB | ||
Filedesc metadata | emd-37210.cif.gz | 6.1 KB | ||
Others | emd_37210_half_map_1.map.gz emd_37210_half_map_2.map.gz | 200.2 MB 200.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37210 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37210 | HTTPS FTP |
-Validation report
Summary document | emd_37210_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_37210_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_37210_validation.xml.gz | 15.6 KB | Display | |
Data in CIF | emd_37210_validation.cif.gz | 18.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37210 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37210 | HTTPS FTP |
-Related structure data
Related structure data | 8kg5MC 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_37210.map.gz / Format: CCP4 / Size: 216 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: 0.73 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37210_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37210_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Prefusion RSV F Bound to Lonafarnib and D25 Fab
Entire | Name: Prefusion RSV F Bound to Lonafarnib and D25 Fab |
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Components |
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-Supramolecule #1: Prefusion RSV F Bound to Lonafarnib and D25 Fab
Supramolecule | Name: Prefusion RSV F Bound to Lonafarnib and D25 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Human respiratory syncytial virus A (strain A2) |
-Macromolecule #1: Fusion glycoprotein F0,Fibritin
Macromolecule | Name: Fusion glycoprotein F0,Fibritin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterobacteria phage T4 (virus) |
Molecular weight | Theoretical: 64.530602 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNA VTELQLLMQS TPATNNRARR ELPRFMNYTL NNAKKTNVTL SKKRKRRFLG FLLGVGSAIA SGVAVCKVLH L EGEVNKIK ...String: MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNA VTELQLLMQS TPATNNRARR ELPRFMNYTL NNAKKTNVTL SKKRKRRFLG FLLGVGSAIA SGVAVCKVLH L EGEVNKIK SALLSTNKAV VSLSNGVSVL TFKVLDLKNY IDKQLLPILN KQSCSISNIE TVIEFQQKNN RLLEITREFS VN AGVTTPV STYMLTNSEL LSLINDMPIT NDQKKLMSNN VQIVRQQSYS IMCIIKEEVL AYVVQLPLYG VIDTPCWKLH TSP LCTTNT KEGSNICLTR TDRGWYCDNA GSVSFFPQAE TCKVQSNRVF CDTMNSLTLP SEVNLCNVDI FNPKYDCKIM TSKT DVSSS VITSLGAIVS CYGKTKCTAS NKNRGIIKTF SNGCDYVSNK GVDTVSVGNT LYYVNKQEGK SLYVKGEPII NFYDP LVFP SDEFDASISQ VNEKINQSLA FIRKSDELLG SGYIPEAPRD GQAYVRKDGE WVFLSTFLSG LEVLFQGPGG WSHPQF EKG GGSGGGSGGS AWSHPQFEKG GS UniProtKB: Fusion glycoprotein F0, Fibritin |
-Macromolecule #2: D25 heavy chain
Macromolecule | Name: D25 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 24.504629 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWLRQA PGQGPEWMGG IIPVLGTVHY APKFQGRVTI TADESTDTAY IHLISLRSE DTAMYYCATE TALVVSTTYL PHYFDNWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN ...String: QVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWLRQA PGQGPEWMGG IIPVLGTVHY APKFQGRVTI TADESTDTAY IHLISLRSE DTAMYYCATE TALVVSTTYL PHYFDNWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF P EPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KVDKKVEPKS CDK |
-Macromolecule #3: D25 light chain
Macromolecule | Name: D25 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.325865 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIQMTQSPSS LSAAVGDRVT ITCQASQDIV NYLNWYQQKP GKAPKLLIYV ASNLETGVPS RFSGSGSGTD FSLTISSLQP EDVATYYCQ QYDNLPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS ...String: DIQMTQSPSS LSAAVGDRVT ITCQASQDIV NYLNWYQQKP GKAPKLLIYV ASNLETGVPS RFSGSGSGTD FSLTISSLQP EDVATYYCQ QYDNLPLTFG GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK VDNALQSGNS Q ESVTEQDS KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC |
-Macromolecule #4: 4-{2-[4-(3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO[5,6]CYCLOHEP...
Macromolecule | Name: 4-{2-[4-(3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDIN-11-YL)PIPERIDIN-1-YL]-2-OXOETHYL}PIPERIDINE-1-CARBOXAMIDE type: ligand / ID: 4 / Number of copies: 3 / Formula: 336 |
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Molecular weight | Theoretical: 638.822 Da |
Chemical component information | ChemComp-336: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 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: 2.4 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 37059 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |