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Yorodumi- PDB-7tjq: SAN27-14 bound to a antigenic site V on prefusion-stabilized hMPV F -
+Open data
-Basic information
Entry | Database: PDB / ID: 7tjq | ||||||
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Title | SAN27-14 bound to a antigenic site V on prefusion-stabilized hMPV F | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / neutralizing antibodies / prefusion-specific antibodies / antigenic site V / hMPV F / VIRAL PROTEIN-IMMUNE SYSTEM complex | ||||||
Function / homology | Precursor fusion glycoprotein F0, Paramyxoviridae / Fusion glycoprotein F0 / fusion of virus membrane with host plasma membrane / host cell plasma membrane / virion membrane / plasma membrane / Fusion glycoprotein F0 Function and homology information | ||||||
Biological species | Homo sapiens (human) Human metapneumovirus | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.13 Å | ||||||
Authors | Hsieh, C.-L. / McLellan, J.S. / Rush, S.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2022 Title: Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus. Authors: Scott A Rush / Gurpreet Brar / Ching-Lin Hsieh / Emilie Chautard / Jennifer N Rainho-Tomko / Chris D Slade / Christine A Bricault / Ana Kume / James Kearns / Rachel Groppo / Sophia T Mundle ...Authors: Scott A Rush / Gurpreet Brar / Ching-Lin Hsieh / Emilie Chautard / Jennifer N Rainho-Tomko / Chris D Slade / Christine A Bricault / Ana Kume / James Kearns / Rachel Groppo / Sophia T Mundle / Linong Zhang / Danilo Casimiro / Tong-Ming Fu / Joshua M DiNapoli / Jason S McLellan / Abstract: Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is ...Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies; however, little is known about the humoral immune response generated from natural infection. Here, using prefusion-stabilized F proteins to interrogate memory B cells from two older adults, we obtain over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal response. Characterization of 136 monoclonal antibodies reveals broad recognition of the protein surface, with potently neutralizing antibodies targeting each antigenic site. Cryo-EM studies further reveal two non-canonical sites and the molecular basis for recognition of the apex of hMPV F by two prefusion-specific neutralizing antibodies. Collectively, these results provide insight into the humoral response to hMPV infection in older adults and will help guide vaccine development. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7tjq.cif.gz | 537.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tjq.ent.gz | 422 KB | Display | PDB format |
PDBx/mmJSON format | 7tjq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7tjq_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7tjq_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7tjq_validation.xml.gz | 67.2 KB | Display | |
Data in CIF | 7tjq_validation.cif.gz | 105.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tj/7tjq ftp://data.pdbj.org/pub/pdb/validation_reports/tj/7tjq | HTTPS FTP |
-Related structure data
Related structure data | 25929MC 7tl0C M: map data used to model this data C: citing same article (ref.) |
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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
-Antibody , 4 types, 12 molecules ADHBELIJNKMO
#1: Antibody | Mass: 13867.521 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #2: Antibody | Mass: 12546.019 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #4: Antibody | Mass: 24201.002 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Antibody | Mass: 22556.883 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Protein / Sugars , 2 types, 9 molecules CFG
#3: Protein | Mass: 60453.852 Da / Num. of mol.: 3 Mutation: Q100R, S101R, L110C, T127C, A140C, N153C, A147C, A185P, L219K, V231I, G294E, N322C, T365C, E453Q, V463C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human metapneumovirus / Production host: Homo sapiens (human) / References: UniProt: H6X1Z0 #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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-Details
Has ligand of interest | N |
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-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: Complex of hMPV F with MPE8 Fab and SAN27-14 Fab / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES | ||||||||||||
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Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||
Buffer solution | pH: 8 Details: 2 mM Tris pH 7.5, 200 mM NaCl, 0.02% NaN3, 0.07% amphipol | ||||||||||||
Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Collected on tilt, CF-1.2-1.3 grids with 0.5 mg/mL DSCavEs2 (2 mM Tris pH 7.5, 200 mM NaCl, 0.02% NaN3, 0.07% amphipol) and 2x fold molar excess MPE8 and 1.5x fold molar excess SAN27-14 ...Details: Collected on tilt, CF-1.2-1.3 grids with 0.5 mg/mL DSCavEs2 (2 mM Tris pH 7.5, 200 mM NaCl, 0.02% NaN3, 0.07% amphipol) and 2x fold molar excess MPE8 and 1.5x fold molar excess SAN27-14 spiked in ~10 minutes before freezing. 3 u of sample was deposited and the grid was plunge frozen using a Vitrobot Mark IV using 4 seconds blot time and -2 force at 100% humidity and 10 C | ||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: C-flat-1.2/1.3 | ||||||||||||
Vitrification | Cryogen name: ETHANE |
-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: 2200 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 3492 |
-Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: SerialEM / Category: image acquisition | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.13 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 93710 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.81 Å2 | ||||||||||||||||||||||||
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