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- EMDB-38564: Structure of Nipah virus Bangladesh string G protein ectodomain t... -

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Entry
Database: EMDB / ID: EMD-38564
TitleStructure of Nipah virus Bangladesh string G protein ectodomain tetramer bound to single-domain antibody n425 at 5.87 Angstroms overall resolution
Map data
Sample
  • Complex: Nipah virus Bangladesh string G protein ectodomain tetramer in complex with single-domain antibody n425
    • Protein or peptide: Nipah virus Bangladesh string G protein
    • Protein or peptide: single-domain antibody n425
KeywordsAntibody / VIRAL PROTEIN
Biological speciesHenipavirus nipahense / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 5.87 Å
AuthorsSun L / Chen Z / Sun Y / Mao Q
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32270984 China
CitationJournal: Nat Commun / Year: 2024
Title: Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein.
Authors: Yulu Wang / Yifang Sun / Zhaoling Shen / Cong Wang / Jun Qian / Qiyu Mao / Yajie Wang / Wenping Song / Yu Kong / Changyou Zhan / Zhenguo Chen / Dimiter S Dimitrov / Zhenlin Yang / Shibo ...Authors: Yulu Wang / Yifang Sun / Zhaoling Shen / Cong Wang / Jun Qian / Qiyu Mao / Yajie Wang / Wenping Song / Yu Kong / Changyou Zhan / Zhenguo Chen / Dimiter S Dimitrov / Zhenlin Yang / Shibo Jiang / Fan Wu / Lu Lu / Tianlei Ying / Lei Sun / Yanling Wu /
Abstract: Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and ...Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.
History
DepositionJan 4, 2024-
Header (metadata) releaseSep 18, 2024-
Map releaseSep 18, 2024-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_38564.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.86 Å/pix.
x 160 pix.
= 298.24 Å
1.86 Å/pix.
x 160 pix.
= 298.24 Å
1.86 Å/pix.
x 160 pix.
= 298.24 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.864 Å
Density
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.0016978161 - 1.2843524
Average (Standard dev.)0.003313942 (±0.037695114)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions160160160
Spacing160160160
CellA=B=C: 298.24 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_38564_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_38564_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Nipah virus Bangladesh string G protein ectodomain tetramer in co...

EntireName: Nipah virus Bangladesh string G protein ectodomain tetramer in complex with single-domain antibody n425
Components
  • Complex: Nipah virus Bangladesh string G protein ectodomain tetramer in complex with single-domain antibody n425
    • Protein or peptide: Nipah virus Bangladesh string G protein
    • Protein or peptide: single-domain antibody n425

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Supramolecule #1: Nipah virus Bangladesh string G protein ectodomain tetramer in co...

SupramoleculeName: Nipah virus Bangladesh string G protein ectodomain tetramer in complex with single-domain antibody n425
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Henipavirus nipahense

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Macromolecule #1: Nipah virus Bangladesh string G protein

MacromoleculeName: Nipah virus Bangladesh string G protein / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Henipavirus nipahense
Molecular weightTheoretical: 67.28475 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MPTESKKVRF ENTASDKGKN PSKVIKSYYG TMDIKKINEG LLDSKILSAF NTVIALLGSI VIIVMNIMII QNYTRCTDNQ AMIKDALQS IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN I SCPNPLPF ...String:
MPTESKKVRF ENTASDKGKN PSKVIKSYYG TMDIKKINEG LLDSKILSAF NTVIALLGSI VIIVMNIMII QNYTRCTDNQ AMIKDALQS IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN I SCPNPLPF REYKPQTEGV SNLVGLPNNI CLQKTSNQIL KPKLISYTLP VVGQSGTCIT DPLLAMDEGY FAYSHLEKIG SC SRGVSKQ RIIGVGEVLD RGDEVPSLFM TNVWTPSNPN TVYHCSAVYN NEFYYVLCAV SVVGDPILNS TYWSGSLMMT RLA VKPKNN GESYNQHQFA LRNIEKGKYD KVMPYGPSGI KQGDTLYFPA VGFLVRTEFT YNDSNCPIAE CQYSKPENCR LSMG IRPNS HYILRSGLLK YNLSDEENSK IVFIEISDQR LSIGSPSKIY DSLGQPVFYQ ASFSWDTMIK FGDVQTVNPL VVNWR DNTV ISRPGQSQCP RFNKCPEVCW EGVYNDAFLI DRINWISAGV FLDSNQTAEN PVFTVFKDNE VLYRAQLASE DTNAQK TIT NCFLLKNKIW CISLVEIYDT GDNVIRPKLF AVKIPEQCT

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Macromolecule #2: single-domain antibody n425

MacromoleculeName: single-domain antibody n425 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 12.764128 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
EVQLVESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSY ISSSSSYTNY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTASYYCARG LAGVWGIDVW GQGTLVTVSS

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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
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Final reconstructionResolution.type: BY AUTHOR / Resolution: 5.87 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 362285
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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