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Yorodumi- EMDB-38563: Structure of Nipah virus Malaysia string G protein ectodomain mon... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38563 | |||||||||
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Title | Structure of Nipah virus Malaysia string G protein ectodomain monomer bound to single-domain antibody n425 at 3.63 Angstroms overall resolution | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Antibody / VIRAL PROTEIN | |||||||||
Function / homology | Function and homology information membrane fusion involved in viral entry into host cell / exo-alpha-sialidase activity / clathrin-dependent endocytosis of virus by host cell / host cell surface receptor binding / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / identical protein binding / membrane Similarity search - Function | |||||||||
Biological species | Henipavirus nipahense / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.63 Å | |||||||||
Authors | Sun L / Chen Z / Sun Y / Mao Q | |||||||||
Funding support | China, 1 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38563.map.gz | 40.3 MB | EMDB map data format | |
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Header (meta data) | emd-38563-v30.xml emd-38563.xml | 15.6 KB 15.6 KB | Display Display | EMDB header |
Images | emd_38563.png | 67.4 KB | ||
Filedesc metadata | emd-38563.cif.gz | 6 KB | ||
Others | emd_38563_half_map_1.map.gz emd_38563_half_map_2.map.gz | 48.9 MB 48.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38563 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38563 | HTTPS FTP |
-Validation report
Summary document | emd_38563_validation.pdf.gz | 642.8 KB | Display | EMDB validaton report |
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Full document | emd_38563_full_validation.pdf.gz | 642.4 KB | Display | |
Data in XML | emd_38563_validation.xml.gz | 12.2 KB | Display | |
Data in CIF | emd_38563_validation.cif.gz | 14.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38563 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38563 | HTTPS FTP |
-Related structure data
Related structure data | 8xpyMC 8xpsC 8xq3C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_38563.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.932 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_38563_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_38563_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Nipah virus Malaysia string G protein ectodomain monomer in compl...
Entire | Name: Nipah virus Malaysia string G protein ectodomain monomer in complex with single-domain antibody n425 |
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Components |
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-Supramolecule #1: Nipah virus Malaysia string G protein ectodomain monomer in compl...
Supramolecule | Name: Nipah virus Malaysia string G protein ectodomain monomer in complex with single-domain antibody n425 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Henipavirus nipahense |
-Macromolecule #1: Glycoprotein G
Macromolecule | Name: Glycoprotein G / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Henipavirus nipahense |
Molecular weight | Theoretical: 67.104703 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MPAENKKVRF ENTTSDKGKI PSKVIKSYYG TMDIKKINEG LLDSKILSAF NTVIALLGSI VIIVMNIMII QNYTRSTDNQ AVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN I SCPNPLPF ...String: MPAENKKVRF ENTTSDKGKI PSKVIKSYYG TMDIKKINEG LLDSKILSAF NTVIALLGSI VIIVMNIMII QNYTRSTDNQ AVIKDALQG IQQQIKGLAD KIGTEIGPKV SLIDTSSTIT IPANIGLLGS KISQSTASIN ENVNEKCKFT LPPLKIHECN I SCPNPLPF REYRPQTEGV SNLVGLPNNI CLQKTSNQIL KPKLISYTLP VVGQSGTCIT DPLLAMDEGY FAYSHLERIG SC SRGVSKQ RIIGVGEVLD RGDEVPSLFM TNVWTPPNPN TVYHCSAVYN NEFYYVLCAV STVGDPILNS TYWSGSLMMT RLA VKPKSN GGGYNQHQLA LRSIEKGRYD KVMPYGPSGI KQGDTLYFPA VGFLVRTEFK YNDSNCPITK CQYSKPENCR LSMG IRPNS HYILRSGLLK YNLSDGENPK VVFIEISDQR LSIGSPSKIY DSLGQPVFYQ ASFSWDTMIK FGDVLTVNPL VVNWR NNTV ISRPGQSQCP RFNTCPEICW EGVYNDAFLI DRINWISAGV FLDSNQTAEN PVFTVFKDNE ILYRAQLASE DTNAQK TIT NCFLLKNKIW CISLVEIYDT GDNVIRPKLF AVKIPEQCT UniProtKB: Glycoprotein G |
-Macromolecule #2: single-domain antibody n425
Macromolecule | Name: single-domain antibody n425 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 12.764128 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGGG LVQPGGSLRL SCAASGFTFS SYAMSWVRQA PGKGLEWVSY ISSSSSYTNY ADSVKGRFTI SRDNSKNTLY LQMNSLRAE DTASYYCARG LAGVWGIDVW GQGTLVTVSS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination 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 |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 661646 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |