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- EMDB-27566: Prefusion-stabilized Nipah virus fusion protein -

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Basic information

Entry
Database: EMDB / ID: EMD-27566
TitlePrefusion-stabilized Nipah virus fusion protein
Map dataPrefusion-stabilized Nipah virus fusion protein
Sample
  • Complex: Prefusion-stabilized Nipah virus fusion protein
    • Protein or peptide: Fusion glycoprotein F0
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsNipah / Nipah virus / NiV / fusion / F / antibody / neutralizing / conserved epitope / neutralizing antibody / prefusion / prefusion-stabilized / vaccine / vaccine design / antigen / antigen design / VIRAL PROTEIN
Function / homology
Function and homology information


membrane fusion involved in viral entry into host cell / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / viral envelope / host cell plasma membrane / virion membrane / membrane
Similarity search - Function
Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0
Similarity search - Domain/homology
Fusion glycoprotein F0
Similarity search - Component
Biological speciesNipah henipavirus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsByrne PO / Blade EG / McLellan JS
Funding support United States, 1 items
OrganizationGrant numberCountry
Welch FoundationF-0003-19620604 United States
CitationJournal: J Virol / Year: 2024
Title: Prefusion stabilization of the Hendra and Langya virus F proteins.
Authors: Patrick O Byrne / Elizabeth G Blade / Brian E Fisher / David R Ambrozak / Ajit R Ramamohan / Barney S Graham / Rebecca J Loomis / Jason S McLellan /
Abstract: Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the genus, NiV and HeV use an attachment (G) glycoprotein and a ...Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks.
History
DepositionJul 11, 2022-
Header (metadata) releaseJul 19, 2023-
Map releaseJul 19, 2023-
UpdateMar 6, 2024-
Current statusMar 6, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27566.png

Downloads & links

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Map

FileDownload / File: emd_27566.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationPrefusion-stabilized Nipah virus fusion protein
Voxel sizeX=Y=Z: 0.94 Å
Density
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-1.7254789 - 2.325077
Average (Standard dev.)-0.00062996964 (±0.04778951)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 282.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_27566_msk_1.map
Projections & Slices
AxesZYX

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Additional map: Additional Map 1

Fileemd_27566_additional_1.map
AnnotationAdditional Map 1
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Additional map: Additional Map 2

Fileemd_27566_additional_2.map
AnnotationAdditional Map 2
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Half map: Half Map 1

Fileemd_27566_half_map_1.map
AnnotationHalf Map 1
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Half map: Half Map 2

Fileemd_27566_half_map_2.map
AnnotationHalf Map 2
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Sample components

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Entire : Prefusion-stabilized Nipah virus fusion protein

EntireName: Prefusion-stabilized Nipah virus fusion protein
Components
  • Complex: Prefusion-stabilized Nipah virus fusion protein
    • Protein or peptide: Fusion glycoprotein F0
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Prefusion-stabilized Nipah virus fusion protein

SupramoleculeName: Prefusion-stabilized Nipah virus fusion protein / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Nipah henipavirus

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Macromolecule #1: Fusion glycoprotein F0

MacromoleculeName: Fusion glycoprotein F0 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Nipah henipavirus
Molecular weightTheoretical: 48.503523 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ILHYEKLSKI GLVKGVTRKY KIKSNPLTKD IVIKMIPNVS NMSQCTGSVM ENYKTRLNGI LTPIKGALEI YKNNTHDCVG DVRLAGVCM AGVAIGIATA AQITAGVALY EAMKNADNIN KLKSSIESTN EAVVKLQETA EKTVYVFTAL QDYINTNLVP T IDKIPCKQ ...String:
ILHYEKLSKI GLVKGVTRKY KIKSNPLTKD IVIKMIPNVS NMSQCTGSVM ENYKTRLNGI LTPIKGALEI YKNNTHDCVG DVRLAGVCM AGVAIGIATA AQITAGVALY EAMKNADNIN KLKSSIESTN EAVVKLQETA EKTVYVFTAL QDYINTNLVP T IDKIPCKQ TELSLDLALS KYLSDLLFVF GPNLQDPVSN SMTIQAISQA FGGNYETLLR TLGYATEDFD DLLESDSITG QI IYVDLSS YYIIVRVYFP ILTEIQQAYI QELLPVSFNN DNSEWISIVP NFILVRNTLI SNIEIGFCLI TKRSVICNQD YAT PMTNNM RECLTGSTEK CPRELVVSSH VPRFALSNGV LFANCISVTC QCQTTGRAIS QSGEQTLLMI DNTTCPTAVL GNVI ISLGK YLGSVNYNSE GIAIGPPVFT DKVDISSQIS SMNQSLQ

UniProtKB: Fusion glycoprotein F0

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Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 12 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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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: 2.5 µm / Nominal defocus min: 1.5 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 447701
FSC plot (resolution estimation)

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