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Yorodumi- EMDB-41825: Prefusion-stabilized Langya virus F protein, variant G99C/I109C -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41825 | |||||||||
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Title | Prefusion-stabilized Langya virus F protein, variant G99C/I109C | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Langya / Langya virus / LayV / fusion / F / LayV F / VIRAL PROTEIN / disulfide / prefusion / prefusion-stabilized / vaccine design / VIRUS | |||||||||
Biological species | Langya virus | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Byrne PO / McLellan JS | |||||||||
Funding support | United States, 1 items
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Citation | Journal: 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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41825.map.gz | 59.8 MB | EMDB map data format | |
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Header (meta data) | emd-41825-v30.xml emd-41825.xml | 16.3 KB 16.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41825_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_41825.png | 84.3 KB | ||
Masks | emd_41825_msk_1.map | 64 MB | Mask map | |
Filedesc metadata | emd-41825.cif.gz | 5.5 KB | ||
Others | emd_41825_additional_1.map.gz emd_41825_half_map_1.map.gz emd_41825_half_map_2.map.gz | 31.8 MB 59.3 MB 59.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41825 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41825 | HTTPS FTP |
-Validation report
Summary document | emd_41825_validation.pdf.gz | 932.7 KB | Display | EMDB validaton report |
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Full document | emd_41825_full_validation.pdf.gz | 932.3 KB | Display | |
Data in XML | emd_41825_validation.xml.gz | 16.4 KB | Display | |
Data in CIF | emd_41825_validation.cif.gz | 21.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41825 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41825 | HTTPS FTP |
-Related structure data
Related structure data | 8u1rMC 8dngC 8dnrC 8do4C M: atomic model generated by this map C: citing same article (ref.) |
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-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_41825.map.gz / Format: CCP4 / Size: 64 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: 0.94 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_41825_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_41825_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_41825_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_41825_half_map_2.map | ||||||||||||
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Density Histograms |
-Sample components
-Entire : Prefusion-stabilized Langya virus F protein, variant G99C/I109C
Entire | Name: Prefusion-stabilized Langya virus F protein, variant G99C/I109C |
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Components |
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-Supramolecule #1: Prefusion-stabilized Langya virus F protein, variant G99C/I109C
Supramolecule | Name: Prefusion-stabilized Langya virus F protein, variant G99C/I109C type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Langya virus |
-Macromolecule #1: Fusion glycoprotein F
Macromolecule | Name: Fusion glycoprotein F / type: protein_or_peptide / ID: 1 Details: Prefusion-stabilized Langya virus F protein, variant G99C/I109C Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Langya virus |
Molecular weight | Theoretical: 60.590789 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAFLKSAIIC YLLFYPHIVK SSLHYDSLSK VGIIKGLTYN YKIKGSPSTK LMVVKLIPNI DGVRNCTQKQ FDEYKNLVKN VLEPVKLAL NAMLDNVKSC NNKYRFAGAC MAGVALGVAT AATVTAGIAL HRSNENAQAI ANMKNAIQNT NEAVKQLQLA N KQTLAVID ...String: MAFLKSAIIC YLLFYPHIVK SSLHYDSLSK VGIIKGLTYN YKIKGSPSTK LMVVKLIPNI DGVRNCTQKQ FDEYKNLVKN VLEPVKLAL NAMLDNVKSC NNKYRFAGAC 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 EDYIEKSEEG GSGYI PEAP RDGQAYVRKD GEWVLLSTFL GRSLEVLFQG PGHHHHHHHH SAWSHPQFEK GGGSGGGGSG GSAWSHPQFE K |
-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 | TFS GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 44.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm |