[English] 日本語
Yorodumi
- PDB-8kg5: Prefusion RSV F Bound to Lonafarnib and D25 Fab -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8kg5
TitlePrefusion RSV F Bound to Lonafarnib and D25 Fab
Components
  • D25 heavy chain
  • D25 light chain
  • Fusion glycoprotein F0,Fibritin
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Respiratory syncytial virus / F protein / Lonafarnib / VIRAL PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


positive regulation of syncytium formation by virus / Translation of respiratory syncytial virus mRNAs / RSV-host interactions / host cell Golgi membrane / Maturation of hRSV A proteins / Assembly and release of respiratory syncytial virus (RSV) virions / Respiratory syncytial virus (RSV) attachment and entry / virion component / entry receptor-mediated virion attachment to host cell / symbiont entry into host cell ...positive regulation of syncytium formation by virus / Translation of respiratory syncytial virus mRNAs / RSV-host interactions / host cell Golgi membrane / Maturation of hRSV A proteins / Assembly and release of respiratory syncytial virus (RSV) virions / 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
Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / Fibritin C-terminal / Fibritin C-terminal region
Similarity search - Domain/homology
Chem-336 / Fusion glycoprotein F0 / Fibritin
Similarity search - Component
Biological speciesHuman respiratory syncytial virus A
Enterobacteria phage T4 (virus)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.17 Å
AuthorsYang, Q. / Xue, B. / Liu, F. / Peng, W. / Chen, X.
Funding support China, 1items
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, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jun 19, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Fusion glycoprotein F0,Fibritin
B: Fusion glycoprotein F0,Fibritin
C: Fusion glycoprotein F0,Fibritin
D: D25 heavy chain
E: D25 light chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)243,3398
Polymers241,4225
Non-polymers1,9163
Water00
1


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

-
Components

#1: Protein Fusion glycoprotein F0,Fibritin / Collar protein / Whisker antigen control 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 D25 heavy chain


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 D25 light chain


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 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 / SCH66336


Mass: 638.822 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C27H31Br2ClN4O2 / Feature type: SUBJECT OF INVESTIGATION / Comment: medication*YM
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Prefusion RSV F Bound to Lonafarnib and D25 Fab / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Human respiratory syncytial virus A (strain A2)11259
31Enterobacteria phage T4 (virus)10665
41Homo sapiens (human)9606
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
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: 2400 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.17 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 37059 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00712407
ELECTRON MICROSCOPYf_angle_d0.91416824
ELECTRON MICROSCOPYf_dihedral_angle_d16.7037544
ELECTRON MICROSCOPYf_chiral_restr0.0542011
ELECTRON MICROSCOPYf_plane_restr0.0052120

+
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://pdbjlvh1.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