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- EMDB-29299: Langya virus F glycoprotein ectodomain in prefusion form -

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Basic information

Entry
Database: EMDB / ID: EMD-29299
TitleLangya virus F glycoprotein ectodomain in prefusion form
Map data
Sample
  • Complex: Langya virus F ectodomain in prefusion form
    • Protein or peptide: Fusion glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsF ectodomain / prefusion / VIRAL PROTEIN
Biological speciesLangya virus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.37 Å
AuthorsLow YS / Isaacs A / Modhiran N / Watterson D
Funding support Australia, 1 items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)GA82108 Australia
CitationJournal: Nat Commun / Year: 2023
Title: Structure and antigenicity of divergent Henipavirus fusion glycoproteins.
Authors: Ariel Isaacs / Yu Shang Low / Kyle L Macauslane / Joy Seitanidou / Cassandra L Pegg / Stacey T M Cheung / Benjamin Liang / Connor A P Scott / Michael J Landsberg / Benjamin L Schulz / Keith ...Authors: Ariel Isaacs / Yu Shang Low / Kyle L Macauslane / Joy Seitanidou / Cassandra L Pegg / Stacey T M Cheung / Benjamin Liang / Connor A P Scott / Michael J Landsberg / Benjamin L Schulz / Keith J Chappell / Naphak Modhiran / Daniel Watterson /
Abstract: In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and ...In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.
History
DepositionDec 26, 2022-
Header (metadata) releaseJun 28, 2023-
Map releaseJun 28, 2023-
UpdateJun 28, 2023-
Current statusJun 28, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_29299.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.09375 Å
Density
Contour LevelBy AUTHOR: 0.09
Minimum - Maximum-0.1872851 - 0.4671166
Average (Standard dev.)0.00091363007 (±0.017109625)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 280.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_29299_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Additional map: Sharpened map

Fileemd_29299_additional_1.map
AnnotationSharpened map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Half map: #2

Fileemd_29299_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Half map: #1

Fileemd_29299_half_map_2.map
Projections & Slices
AxesZYX

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Sample components

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Entire : Langya virus F ectodomain in prefusion form

EntireName: Langya virus F ectodomain in prefusion form
Components
  • Complex: Langya virus F ectodomain in prefusion form
    • Protein or peptide: Fusion glycoprotein
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Langya virus F ectodomain in prefusion form

SupramoleculeName: Langya virus F ectodomain in prefusion form / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Langya virus
Molecular weightTheoretical: 200 KDa

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Macromolecule #1: Fusion glycoprotein

MacromoleculeName: Fusion glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Langya virus
Molecular weightTheoretical: 52.297793 KDa
Recombinant expressionOrganism: Cricetulus griseus (Chinese hamster)
SequenceString: MAFLKSAIIC YLLFYPHIVK SSLHYDSLSK VGIIKGLTYN YKIKGSPSTK LMVVKLIPNI DGVRNCTQKQ FDEYKNLVKN VLEPVKLAL NAMLDNVKSG NNKYRFAGAI MAGVALGVAT AATVTAGIAL HRSNENAQAI ANMKNAIQNT NEAVKQLQLA N KQTLAVID ...String:
MAFLKSAIIC YLLFYPHIVK SSLHYDSLSK VGIIKGLTYN YKIKGSPSTK LMVVKLIPNI DGVRNCTQKQ FDEYKNLVKN VLEPVKLAL NAMLDNVKSG NNKYRFAGAI MAGVALGVAT AATVTAGIAL HRSNENAQAI ANMKNAIQNT NEAVKQLQLA N KQTLAVID TIRGEINNNI IPVINQLSCD TIGLSVGIKL TQYYSEILTA FGPALQNPVN TRITIQAISS VFNRNFDELL KI MGYTSGD LYEILHSGLI RGNIIDVDVE AGYIALEIEF PNLTLVPNAV VQELMPISYN VDGDEWVTLV PRFVLTRTTL LSN IDTSRC TVTESSVICD NDYALPMSYE LIGCLQGDTS KCAREKVVSS YVPRFALSDG LVYANCLNTI CRCMDTDTPI SQSL GTTVS LLDNKKCLVY QVGDILISVG SYLGEGEYSA DNVELGPPVV IDKIDIGNQL AGINQTLQNA EDYIEKSEEF LKG

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Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 3 / 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

Concentration0.7 mg/mL
BufferpH: 6.8
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Instrument: LEICA EM GP
Details0.255% CHAPS added

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Electron microscopy

MicroscopeJEOL CRYO ARM 300
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 40.0 µm / Calibrated magnification: 60000 / Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 25.0 µm / Nominal defocus min: 5.0 µm / Nominal magnification: 60000
Specialist opticsEnergy filter - Name: In-column Omega Filter / Energy filter - Slit width: 20 eV
Sample stageSpecimen holder model: JEOL CRYOSPECPORTER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2

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Image processing

Particle selectionNumber selected: 631827
Startup modelType of model: OTHER / Details: Ab initio reconstruction, maximum likelihood
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.1)
Final 3D classificationNumber classes: 2 / Avg.num./class: 29400 / Software - Name: cryoSPARC (ver. 3.3.1)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.3.1)
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.37 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.3.1) / Number images used: 25475
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementSpace: REAL / Protocol: FLEXIBLE FIT / Overall B value: 88.4 / Target criteria: Molprobity
Output model

PDB-8fmx:
Langya virus F glycoprotein ectodomain in prefusion form

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