+Open data
-Basic information
Entry | Database: PDB / ID: 7tl0 | ||||||
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Title | Cryo-EM structure of hMPV preF bound by Fabs MPE8 and SAN32-2 | ||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / neutralizing antibody / fusion protein / metapneumovirus / site 0 / 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 | Human metapneumovirus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.06 Å | ||||||
Authors | Rush, S.A. / Hsieh, C.-L. / McLellan, J.S. | ||||||
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 | 7tl0.cif.gz | 845.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tl0.ent.gz | 705.6 KB | Display | PDB format |
PDBx/mmJSON format | 7tl0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7tl0_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7tl0_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7tl0_validation.xml.gz | 66.3 KB | Display | |
Data in CIF | 7tl0_validation.cif.gz | 103.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tl/7tl0 ftp://data.pdbj.org/pub/pdb/validation_reports/tl/7tl0 | HTTPS FTP |
-Related structure data
Related structure data | 25982MC 7tjqC 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 , 1 types, 3 molecules ABC
#1: 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 |
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-Antibody , 4 types, 12 molecules DFHEGIJLNKMO
#2: Antibody | Mass: 24099.031 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 23542.988 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: 23985.793 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: 22772.092 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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-Sugars , 2 types, 9 molecules
#6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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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: Trimeric prefusion hMPV F glycoprotein bound by three molecules of Fabs SAN32-2 and MPE8 Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES | |||||||||||||||||||||||||
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Molecular weight | Value: 457.9 kDa/nm / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: C-flat-1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283.15 K |
-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 magnification: 29000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3636 |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 772860 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.06 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 134989 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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