[English] 日本語
Yorodumi
- EMDB-37210: Prefusion RSV F Bound to Lonafarnib and D25 Fab -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-37210
TitlePrefusion RSV F Bound to Lonafarnib and D25 Fab
Map data
Sample
  • Complex: Prefusion RSV F Bound to Lonafarnib and D25 Fab
    • Protein or peptide: Fusion glycoprotein F0,Fibritin
    • Protein or peptide: D25 heavy chain
    • Protein or peptide: D25 light chain
  • Ligand: 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
KeywordsRespiratory syncytial virus / F protein / Lonafarnib / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


positive regulation of syncytium formation by virus / Assembly and release of respiratory syncytial virus (RSV) virions / Translation of respiratory syncytial virus mRNAs / Respiratory syncytial virus (RSV) attachment and entry / RSV-host interactions / Maturation of hRSV A proteins / host cell Golgi membrane / virion component / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell ...positive regulation of syncytium formation by virus / Assembly and release of respiratory syncytial virus (RSV) virions / Translation of respiratory syncytial virus mRNAs / Respiratory syncytial virus (RSV) attachment and entry / RSV-host interactions / Maturation of hRSV A proteins / host cell Golgi membrane / 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
Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / Fibritin C-terminal / Fibritin C-terminal region
Similarity search - Domain/homology
Fusion glycoprotein F0 / Fibritin
Similarity search - Component
Biological speciesHuman respiratory syncytial virus A (strain A2) / Enterobacteria phage T4 (virus) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.17 Å
AuthorsYang Q / Xue B / Liu F / Peng W / Chen X
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32000111 China
CitationJournal: 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
DepositionAug 17, 2023-
Header (metadata) releaseJun 19, 2024-
Map releaseJun 19, 2024-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_37210.png

Downloads & links

-
Map

FileDownload / File: emd_37210.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 384 pix.
= 280.32 Å		0.73 Å/pix.
x 384 pix.
= 280.32 Å		0.73 Å/pix.
x 384 pix.
= 280.32 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.73 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.47712252 - 0.7393384
Average (Standard dev.)0.0006844678 (±0.0197544)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 280.32 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_37210_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_37210_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Prefusion RSV F Bound to Lonafarnib and D25 Fab

EntireName: Prefusion RSV F Bound to Lonafarnib and D25 Fab
Components
  • Complex: Prefusion RSV F Bound to Lonafarnib and D25 Fab
    • Protein or peptide: Fusion glycoprotein F0,Fibritin
    • Protein or peptide: D25 heavy chain
    • Protein or peptide: D25 light chain
  • Ligand: 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

-
Supramolecule #1: Prefusion RSV F Bound to Lonafarnib and D25 Fab

SupramoleculeName: Prefusion RSV F Bound to Lonafarnib and D25 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Human respiratory syncytial virus A (strain A2)

-
Macromolecule #1: Fusion glycoprotein F0,Fibritin

MacromoleculeName: Fusion glycoprotein F0,Fibritin / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Enterobacteria phage T4 (virus)
Molecular weightTheoretical: 64.530602 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

MacromoleculeName: D25 heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.504629 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

MacromoleculeName: D25 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.325865 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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...

MacromoleculeName: 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
Molecular weightTheoretical: 638.822 Da
Chemical component information

ChemComp-336:
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 / medication*YM / Lonafarnib

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.2 µm
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: INSILICO MODEL
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 37059

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more