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- PDB-8tqk: Human parainfluenza virus type 3 prefusion F trimer in complex wi... -

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Basic information

Entry
Database: PDB / ID: 8tqk
TitleHuman parainfluenza virus type 3 prefusion F trimer in complex with rPIV3-18 Fab
Components
  • Fusion glycoprotein F0
  • Heavy chain Fab rPIV3-18
  • Light chain Fab rPIV3-28
KeywordsVIRAL PROTEIN / IMMUNE SYSTEM / viral neutralization
Function / homologyPrecursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / host cell plasma membrane / virion membrane / membrane / Fusion glycoprotein F0
Function and homology information
Biological speciesHomo sapiens (human)
Human respirovirus 3
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsOtrelo-Cardoso, A.R. / Jardetzky, T.S.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 AI13752 United States
CitationJournal: Nat Microbiol / Year: 2024
Title: Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies.
Authors: Naveenchandra Suryadevara / Ana Rita Otrelo-Cardoso / Nurgun Kose / Yao-Xiong Hu / Elad Binshtein / Rachael M Wolters / Alexander L Greninger / Laura S Handal / Robert H Carnahan / Anne ...Authors: Naveenchandra Suryadevara / Ana Rita Otrelo-Cardoso / Nurgun Kose / Yao-Xiong Hu / Elad Binshtein / Rachael M Wolters / Alexander L Greninger / Laura S Handal / Robert H Carnahan / Anne Moscona / Theodore S Jardetzky / James E Crowe /
Abstract: Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have ...Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs.
History
DepositionAug 7, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 24, 2024Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
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Revision 1.0Apr 24, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
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Revision 1.0Apr 24, 2024Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
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Revision 1.0Apr 24, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 24, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update
Revision 1.2Nov 6, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Revision 1.3May 14, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1May 14, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
D: Heavy chain Fab rPIV3-18
E: Light chain Fab rPIV3-28
F: Heavy chain Fab rPIV3-18
G: Light chain Fab rPIV3-28
H: Heavy chain Fab rPIV3-18
L: Light chain Fab rPIV3-28
A: Fusion glycoprotein F0
B: Fusion glycoprotein F0
C: Fusion glycoprotein F0


Theoretical massNumber of molelcules
Total (without water)314,9749
Polymers314,9749
Non-polymers00
Water00
1


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

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Components

#1: Antibody Heavy chain Fab rPIV3-18


Mass: 23959.973 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#2: Antibody Light chain Fab rPIV3-28


Mass: 23671.273 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#3: Protein Fusion glycoprotein F0


Mass: 57360.102 Da / Num. of mol.: 3 / Mutation: Q162C, L168C, I213C, G230C, A463V, I474Y
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human respirovirus 3 / Gene: F, KMQ_34898gpF / Production host: Homo sapiens (human) / References: UniProt: A0A059QA82
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

Component
IDNameTypeEntity IDParent-IDSource
1HPIV3 prefusion F trimer in complex with rPIV3-18 FabCOMPLEXall0MULTIPLE SOURCES
2Fusion glycoprotein F0COMPLEX#31RECOMBINANT
3rPIV3-18 light chainCOMPLEX#21RECOMBINANT
4rPIV3-18 heavy chainCOMPLEX#11RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Human respirovirus 311216
32Human respirovirus 311216
43Homo sapiens (human)9606
54Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDStrainCellPlasmid
21Homo sapiens (human)9606293 6eHEKPTT5
32Homo sapiens (human)9606293 6eHEKPTT5
43Cricetulus griseus (Chinese hamster)10029CHO
54Cricetulus griseus (Chinese hamster)10029CHO
Buffer solutionpH: 7.4
SpecimenConc.: 1.15 mg/ml / Embedding 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: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm
Specimen holderSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.20.1_4487: / Classification: refinement
EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 278016 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00314955
ELECTRON MICROSCOPYf_angle_d0.62120266
ELECTRON MICROSCOPYf_dihedral_angle_d4.7742037
ELECTRON MICROSCOPYf_chiral_restr0.0422388
ELECTRON MICROSCOPYf_plane_restr0.0052560

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