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Open data
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Basic information
Entry | ![]() | |||||||||||||||
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Title | Rabies virus glycoprotein trimer | |||||||||||||||
![]() | RABVG pre-fusion trimer with no interacting fusion loops | |||||||||||||||
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![]() | Rabies virus glycoprotein / antibodies / viral fusion protein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.92 Å | |||||||||||||||
![]() | Callaway HM / Zyla D / Larrous F / Dias de Melo G / Hastie KM / Avalos RD / Agarwal A / Bouhry H / Corti D / Saphire EO | |||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Authors: Heather M Callaway / Dawid Zyla / Florence Larrous / Guilherme Dias de Melo / Kathryn M Hastie / Ruben Diaz Avalos / Alyssa Agarwal / Davide Corti / Hervé Bourhy / Erica Ollmann Saphire / ![]() ![]() ![]() Abstract: Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but ...Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39 Å cryo-electron microscopy structure of trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central α helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis from which to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.6 KB 19.6 KB | Display Display | ![]() |
Images | ![]() | 472.8 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 4.7 MB 4.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | RABVG pre-fusion trimer with no interacting fusion loops | ||||||||||||||||||||
Voxel size | X=Y=Z: 2.67636 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Map Half 1
File | emd_26398_half_map_1.map | ||||||||||||
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Annotation | Map Half 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Hap Half 2
File | emd_26398_half_map_2.map | ||||||||||||
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Annotation | Hap Half 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Rabies virus glycoprotein pre-fusion trimer in complex with neutr...
Entire | Name: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122 |
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Components |
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-Supramolecule #1: Rabies virus glycoprotein pre-fusion trimer in complex with neutr...
Supramolecule | Name: Rabies virus glycoprotein pre-fusion trimer in complex with neutralizing antibody RVA122 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: Reconstruction with no interacting fusion loops |
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-Macromolecule #1: Glycoprotein
Macromolecule | Name: Glycoprotein / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: MVPQALLFVP LLVFPLCFGK FPIYTIPDKL GPWSPIDIHH LSCPNNLVVE DEGCTNLSGF SYMELKVGYI SAIKMNGFTC TGVVTEAET YTNFVGYVTT TFKRKHFRPT PDACRAAYNW KMAGDPRYEE SLHNPYPDYH WLRTVKTTKE SLVIISPSVA D LDPYDRSL ...String: MVPQALLFVP LLVFPLCFGK FPIYTIPDKL GPWSPIDIHH LSCPNNLVVE DEGCTNLSGF SYMELKVGYI SAIKMNGFTC TGVVTEAET YTNFVGYVTT TFKRKHFRPT PDACRAAYNW KMAGDPRYEE SLHNPYPDYH WLRTVKTTKE SLVIISPSVA D LDPYDRSL HSRVFPGGNC SGVAVSSTYC STNHDYTIWM PENPRLGMSC DIFTNSRGKR ASKGSETCGF VDERGLYKSL KG ACKLKLC GVLGLRLMDG TWVAMQTSNE TKWCPPGQLV NLHDFRSDEI EHLVVEELVK KREECLDALE SIMTTKSVSF RRL SHLRKL VPGFGKAYTI FNKTLMEADA HYKSVRTWNE IIPSKGCLRV GGRCHPHVNG VFFNGIILGP DGNVLIPEMQ SSLL QQHME LLVSSVIPLM HPLADPSTVF KNGDEAEDFV EVHL |
-Macromolecule #2: RVA122 Fab Light Chain
Macromolecule | Name: RVA122 Fab Light Chain / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QSVLTQSPSA SDTPGQRVTI SCSGSSSNIG SNYVYWYQQF PGTAPKLLIY KSDKRPSGVP DRFSGSTSGT SASLAISGLR SEDEADYYC AAWDNRLSGW LFGGGTKLTV LGTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS G NSQESVTE ...String: QSVLTQSPSA SDTPGQRVTI SCSGSSSNIG SNYVYWYQQF PGTAPKLLIY KSDKRPSGVP DRFSGSTSGT SASLAISGLR SEDEADYYC AAWDNRLSGW LFGGGTKLTV LGTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV QWKVDNALQS G NSQESVTE QDSKDSTYSL SSTLTLSKAD YEKHKVYACE VTHQGLRSPV TKSFNRGEC |
-Macromolecule #3: RVA122 Fab Heavy Chain
Macromolecule | Name: RVA122 Fab Heavy Chain / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVHLQESGPG LVKPSETLSL TCTVSGDSMN NFYWGWIRQP AGKGLEWIGY IYYSGTTNYN PSLKSRVTIS IDTSKNQFSL KVNSVTAAD TAVYYCARDS GDYVSYYYYG MDVWGPGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String: QVHLQESGPG LVKPSETLSL TCTVSGDSMN NFYWGWIRQP AGKGLEWIGY IYYSGTTNYN PSLKSRVTIS IDTSKNQFSL KVNSVTAAD TAVYYCARDS GDYVSYYYYG MDVWGPGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSCDL EVDDDDKAGW SH PQFEKGG GSGGGSGGGS WSHPQFEK |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL | ||||||||||||||||||
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Buffer | pH: 7.4 Component:
Details: PBS pH 7.4 with 0.03mM LMNG | ||||||||||||||||||
Grid | Model: C-flat-1.2/1.3 | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K2 BASE (4k x 4k) / Average electron dose: 26.74 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |