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Yorodumi- PDB-8dbz: CryoEM structure of Hantavirus ANDV Gn(H) protein complex with 2F... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dbz | ||||||
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Title | CryoEM structure of Hantavirus ANDV Gn(H) protein complex with 2Fabs ANDV-5 and ANDV-34 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Fab / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / immunoglobulin complex, circulating / immunoglobulin receptor binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / complement activation, classical pathway / antigen binding / endocytosis involved in viral entry into host cell / antibacterial humoral response ...symbiont-mediated suppression of host TRAF-mediated signal transduction / host cell Golgi membrane / host cell mitochondrion / immunoglobulin complex, circulating / immunoglobulin receptor binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / complement activation, classical pathway / antigen binding / endocytosis involved in viral entry into host cell / antibacterial humoral response / host cell surface / host cell endoplasmic reticulum membrane / blood microparticle / induction by virus of host autophagy / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / virion membrane / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Andes orthohantavirus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||
Authors | Binshtein, E. / Crowe, J.E. | ||||||
Funding support | United States, 1items
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Citation | Journal: Elife / Year: 2023 Title: Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies. Authors: Taylor B Engdahl / Elad Binshtein / Rebecca L Brocato / Natalia A Kuzmina / Lucia M Principe / Steven A Kwilas / Robert K Kim / Nathaniel S Chapman / Monique S Porter / Pablo Guardado-Calvo ...Authors: Taylor B Engdahl / Elad Binshtein / Rebecca L Brocato / Natalia A Kuzmina / Lucia M Principe / Steven A Kwilas / Robert K Kim / Nathaniel S Chapman / Monique S Porter / Pablo Guardado-Calvo / Félix A Rey / Laura S Handal / Summer M Diaz / Irene A Zagol-Ikapitte / Minh H Tran / W Hayes McDonald / Jens Meiler / Joseph X Reidy / Andrew Trivette / Alexander Bukreyev / Jay W Hooper / James E Crowe / Abstract: Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are ...Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dbz.cif.gz | 194.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dbz.ent.gz | 150.4 KB | Display | PDB format |
PDBx/mmJSON format | 8dbz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dbz_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8dbz_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8dbz_validation.xml.gz | 42.7 KB | Display | |
Data in CIF | 8dbz_validation.cif.gz | 66.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/db/8dbz ftp://data.pdbj.org/pub/pdb/validation_reports/db/8dbz | HTTPS FTP |
-Related structure data
Related structure data | 27318MC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 3 molecules AFH
#1: Protein | Mass: 38767.207 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Andes orthohantavirus / Gene: GP, ADT63_77597gpM, ADT63_77598gpM / Production host: Homo sapiens (human) / References: UniProt: Q9E006 |
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#6: Protein | Mass: 10585.920 Da / Num. of mol.: 2 / Fragment: UNP residues 120-222 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: UniProt: P0DOX5 |
-Antibody , 5 types, 6 molecules DEBCGI
#2: Antibody | Mass: 13609.076 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#3: Antibody | Mass: 11912.240 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#4: Antibody | Mass: 14013.572 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#5: Antibody | Mass: 12187.647 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
#7: Antibody | Mass: 11848.126 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Gn(H) in complex with Fabs ANDV-5 ANDV-34 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293.15 K |
-Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / Alignment procedure: ZEMLIN TABLEAU |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 4.34 sec. / Electron dose: 50.86 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3110 |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 208851 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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