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Yorodumi- PDB-8gav: Structure of human NDS.3 Fab in complex with influenza virus neur... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8gav | ||||||
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Title | Structure of human NDS.3 Fab in complex with influenza virus neuraminidase from A/Darwin/09/2021 (H3N2) | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / neuraminidase / antibody / influenza / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information exo-alpha-(2->3)-sialidase activity / exo-alpha-(2->6)-sialidase activity / exo-alpha-(2->8)-sialidase activity / exo-alpha-sialidase / viral budding from plasma membrane / carbohydrate metabolic process / host cell plasma membrane / virion membrane / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | Influenza A virus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
Authors | Tsybovsky, Y. / Lederhofer, J. / Kwong, P.D. / Kanekiyo, M. | ||||||
Funding support | 1items
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Citation | Journal: Immunity / Year: 2024 Title: Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase. Authors: Julia Lederhofer / Yaroslav Tsybovsky / Lam Nguyen / Julie E Raab / Adrian Creanga / Tyler Stephens / Rebecca A Gillespie / Hubza Z Syeda / Brian E Fisher / Michelle Skertic / Christina Yap ...Authors: Julia Lederhofer / Yaroslav Tsybovsky / Lam Nguyen / Julie E Raab / Adrian Creanga / Tyler Stephens / Rebecca A Gillespie / Hubza Z Syeda / Brian E Fisher / Michelle Skertic / Christina Yap / Andrew J Schaub / Reda Rawi / Peter D Kwong / Barney S Graham / Adrian B McDermott / Sarah F Andrews / Neil P King / Masaru Kanekiyo / Abstract: Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the ...Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the NA antigenic landscape still remains incomplete. Here, we describe NA-specific human antibodies that target the underside of the NA globular head domain, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses, and confer both pre- and post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures of two such antibodies in complex with NA reveal non-overlapping epitopes covering the underside of the NA head. These sites are highly conserved among N2 NAs yet inaccessible unless the NA head tilts or dissociates. Our findings help guide the development of effective countermeasures against ever-changing influenza viruses by identifying hidden conserved sites of vulnerability on the NA underside. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8gav.cif.gz | 127 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8gav.ent.gz | 92 KB | Display | PDB format |
PDBx/mmJSON format | 8gav.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8gav_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8gav_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8gav_validation.xml.gz | 34 KB | Display | |
Data in CIF | 8gav_validation.cif.gz | 49.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ga/8gav ftp://data.pdbj.org/pub/pdb/validation_reports/ga/8gav | HTTPS FTP |
-Related structure data
Related structure data | 29909MC 8gatC 8gauC 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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Symmetry | Point symmetry: (Schoenflies symbol: C4 (4 fold cyclic)) |
-Components
#1: Protein | Mass: 51972.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Influenza A virus / Strain: A/Darwin/09/2021 (H3N2) / Gene: NA / Cell line (production host): Expi293 / Production host: Homo sapiens (human) / References: UniProt: A0A8F5JTQ6 | ||
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#2: Antibody | Mass: 24209.240 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293 / Production host: Homo sapiens (human) | ||
#3: Antibody | Mass: 22863.139 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): Expi293 / Production host: Homo sapiens (human) | ||
#4: Sugar | Has ligand of interest | N | |
-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: Influenza virus neuraminidase from A/Darwin/09/2021 (H3N2) in complex with Fab NDS.3 Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES |
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Molecular weight | Value: 0.380 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Expi293 |
Buffer solution | pH: 7 |
Specimen | Conc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: NITROGEN |
-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 / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.12_2829: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: SerialEM / Version: 4.09 / Category: image acquisition | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1066523 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C4 (4 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 247374 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: BACKBONE TRACE / Space: REAL | ||||||||||||||||||||||||
Atomic model building | Source name: SwissModel / Type: in silico model | ||||||||||||||||||||||||
Refine LS restraints |
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