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Yorodumi- PDB-7nrh: Hantaan virus glycoprotein (Gn) in complex with Fab fragment HTN-Gn1. -
+Open data
-Basic information
Entry | Database: PDB / ID: 7nrh | ||||||
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Title | Hantaan virus glycoprotein (Gn) in complex with Fab fragment HTN-Gn1. | ||||||
Components |
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Keywords | VIRUS LIKE PARTICLE / VLP / virus-like particle / Hantaan / HTNV / HNTV / glycoprotein / spike / fab / HTN-Gn1 / antibody / epitope | ||||||
Function / homology | Function and homology information symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host innate immune response / virus-mediated perturbation of host defense response / virion membrane / cell surface / signal transduction ...symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / host cell surface / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host innate immune response / virus-mediated perturbation of host defense response / virion membrane / cell surface / signal transduction / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | Oryctolagus cuniculus (rabbit) Hantaan orthohantavirus | ||||||
Method | ELECTRON MICROSCOPY / subtomogram averaging / cryo EM / Resolution: 19 Å | ||||||
Authors | Stass, R. / Rissanen, I. / Bowden, T.A. / Huiskonen, J.T. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: mBio / Year: 2021 Title: Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen. Authors: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / ...Authors: Ilona Rissanen / Stefanie A Krumm / Robert Stass / Annalis Whitaker / James E Voss / Emily A Bruce / Sylvia Rothenberger / Stefan Kunz / Dennis R Burton / Juha T Huiskonen / Jason W Botten / Thomas A Bowden / Katie J Doores / Abstract: Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two ...Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nnHTN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nnHTN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7nrh.cif.gz | 312.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7nrh.ent.gz | 264.3 KB | Display | PDB format |
PDBx/mmJSON format | 7nrh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7nrh_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7nrh_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7nrh_validation.xml.gz | 28.7 KB | Display | |
Data in CIF | 7nrh_validation.cif.gz | 43.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nr/7nrh ftp://data.pdbj.org/pub/pdb/validation_reports/nr/7nrh | HTTPS FTP |
-Related structure data
Related structure data | 12544MC 7nksC 7o9sC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Antibody | Mass: 24284.264 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Production host: Homo sapiens (human) |
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#2: Antibody | Mass: 22943.162 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Oryctolagus cuniculus (rabbit) / Production host: Homo sapiens (human) |
#3: Protein | Mass: 40350.871 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Hantaan orthohantavirus / Production host: Homo sapiens (human) / References: UniProt: A0A077D153 |
#4: Polysaccharide | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: subtomogram averaging |
-Sample preparation
Component | Name: Hantaan orthohantavirus / Type: VIRUS / Entity ID: #1-#3 / Source: RECOMBINANT |
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Source (natural) | Organism: Hantaan orthohantavirus |
Source (recombinant) | Organism: Homo sapiens (human) |
Details of virus | Empty: YES / Enveloped: YES / Isolate: SPECIES / Type: VIRUS-LIKE PARTICLE |
Buffer solution | pH: 7.5 / Details: PBS |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 4.77 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software | Name: Dynamo / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING ONLY |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 19 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 2380 / Symmetry type: POINT |
EM volume selection | Num. of tomograms: 42 / Num. of volumes extracted: 34460 |