+Open data
-Basic information
Entry | Database: PDB / ID: 7z1h | ||||||
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Title | VAR2CSA APO | ||||||
Components | VAR2CSA APO | ||||||
Keywords | CELL ADHESION / VAR2CSA / malaria | ||||||
Function / homology | Function and homology information | ||||||
Biological species | Plasmodium falciparum (malaria parasite P. falciparum) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.12 Å | ||||||
Authors | Raghavan, S.S.R. / Wang, K.T. | ||||||
Funding support | 1items
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Citation | Journal: PLoS Pathog / Year: 2022 Title: Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA. Authors: Sai Sundar Rajan Raghavan / Robert Dagil / Mary Lopez-Perez / Julian Conrad / Maria Rosaria Bassi / Maria Del Pilar Quintana / Swati Choudhary / Tobias Gustavsson / Yong Wang / Pontus ...Authors: Sai Sundar Rajan Raghavan / Robert Dagil / Mary Lopez-Perez / Julian Conrad / Maria Rosaria Bassi / Maria Del Pilar Quintana / Swati Choudhary / Tobias Gustavsson / Yong Wang / Pontus Gourdon / Michael Fokuo Ofori / Sebastian Boje Christensen / Daniel Thomas Remias Minja / Christentze Schmiegelow / Morten Agertoug Nielsen / Lea Barfod / Lars Hviid / Ali Salanti / Thomas Lavstsen / Kaituo Wang / Abstract: Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. ...Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4's broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7z1h.cif.gz | 341 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7z1h.ent.gz | 272.3 KB | Display | PDB format |
PDBx/mmJSON format | 7z1h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7z1h_validation.pdf.gz | 826.5 KB | Display | wwPDB validaton report |
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Full document | 7z1h_full_validation.pdf.gz | 878.6 KB | Display | |
Data in XML | 7z1h_validation.xml.gz | 66.4 KB | Display | |
Data in CIF | 7z1h_validation.cif.gz | 98.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z1/7z1h ftp://data.pdbj.org/pub/pdb/validation_reports/z1/7z1h | HTTPS FTP |
-Related structure data
Related structure data | 14446MC 7z12C 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
#1: Protein | Mass: 235359.453 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum) Strain: FVO / Gene: PFFVO_03259 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A024V5I6 |
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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: VAR2CSA APO / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.31 MDa / Experimental value: NO |
Source (natural) | Organism: Plasmodium falciparum (malaria parasite P. falciparum) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) |
-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 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.12 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 207129 / Symmetry type: POINT | ||||||||||||||||||||||||
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