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Yorodumi- EMDB-22089: CryoEM structure of the Plasmodium berghei circumsporozoite prote... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22089 | |||||||||||||||
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Title | CryoEM structure of the Plasmodium berghei circumsporozoite protein in complex with inhibitory mouse antibody 3D11. | |||||||||||||||
Map data | Circumsporozoite protein in complex with inhibitory antibody 3D11. | |||||||||||||||
Sample |
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Function / homology | Plasmodium circumsporozoite protein / Thrombospondin type 1 domain / Thrombospondin type-1 (TSP1) repeat superfamily / Thrombospondin type-1 (TSP1) repeat profile. / Thrombospondin type 1 repeats / Thrombospondin type-1 (TSP1) repeat / cell surface / Circumsporozoite protein / Circumsporozoite protein Function and homology information | |||||||||||||||
Biological species | Mus musculus (house mouse) / Plasmodiidae sp. (eukaryote) / Plasmodium berghei (eukaryote) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||
Authors | Kucharska I / Thai E / Rubinstein J / Julien JP | |||||||||||||||
Funding support | Canada, 4 items
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Citation | Journal: Elife / Year: 2020 Title: Structural ordering of the circumsporozoite protein repeats by inhibitory antibody 3D11. Authors: Iga Kucharska / Elaine Thai / Ananya Srivastava / John L Rubinstein / Régis Pomès / Jean-Philippe Julien / Abstract: Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, ...Plasmodium sporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 - the leading malaria vaccine against (Pf) - has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of other Plasmodium species via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding to CSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats of Plasmodium sporozoites. | |||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22089.map.gz | 110.2 MB | EMDB map data format | |
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Header (meta data) | emd-22089-v30.xml emd-22089.xml | 15.8 KB 15.8 KB | Display Display | EMDB header |
Images | emd_22089.png | 350.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22089 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22089 | HTTPS FTP |
-Validation report
Summary document | emd_22089_validation.pdf.gz | 445 KB | Display | EMDB validaton report |
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Full document | emd_22089_full_validation.pdf.gz | 444.5 KB | Display | |
Data in XML | emd_22089_validation.xml.gz | 6.9 KB | Display | |
Data in CIF | emd_22089_validation.cif.gz | 7.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22089 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22089 | HTTPS FTP |
-Related structure data
Related structure data | 6x87MC 6x8pC 6x8qC 6x8sC 6x8uC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_22089.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Circumsporozoite protein in complex with inhibitory antibody 3D11. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Complex of Plasmodium berghei CSP protein and 3D11 Fab
Entire | Name: Complex of Plasmodium berghei CSP protein and 3D11 Fab |
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Components |
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-Supramolecule #1: Complex of Plasmodium berghei CSP protein and 3D11 Fab
Supramolecule | Name: Complex of Plasmodium berghei CSP protein and 3D11 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: 3D11 Fab heavy chain, 3D11 Fab kappa chain
Supramolecule | Name: 3D11 Fab heavy chain, 3D11 Fab kappa chain / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Mus musculus (house mouse) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: Circumsporozoite protein
Supramolecule | Name: Circumsporozoite protein / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Plasmodiidae sp. (eukaryote) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: 3D11 Fab heavy chain
Macromolecule | Name: 3D11 Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 22.830475 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NSQAYLQQSG AELVRSGASV KMSCKASGYT FTSYNMHWVK QTPGQGLEWI GYIYPGNGVT NFNQKFKGKA TLTADTSSST AYMQISSLT SEDSAVYFCA SAAYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA L TSGVHTFP ...String: NSQAYLQQSG AELVRSGASV KMSCKASGYT FTSYNMHWVK QTPGQGLEWI GYIYPGNGVT NFNQKFKGKA TLTADTSSST AYMQISSLT SEDSAVYFCA SAAYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE PVTVSWNSGA L TSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSC |
-Macromolecule #2: 3D11 Fab kappa chain
Macromolecule | Name: 3D11 Fab kappa chain / type: protein_or_peptide / ID: 2 / Number of copies: 7 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 24.19102 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: NSDVVMTQTP LTLSVTIGQP ASISCKSSQS LLYSDGKTYL NWLLQRPGQS PKRLISLVSE LDSGVPDRFT GSGSGTDFTL KISRVEAED LGVYYCWQGT HFPRTFGGGT KLEIKRTVAA PSVFIFPPSD EQLKSGTASV VCLLNNFYPR EAKVQWKVDN A LQSGNSQE ...String: NSDVVMTQTP LTLSVTIGQP ASISCKSSQS LLYSDGKTYL NWLLQRPGQS PKRLISLVSE LDSGVPDRFT GSGSGTDFTL KISRVEAED LGVYYCWQGT HFPRTFGGGT KLEIKRTVAA PSVFIFPPSD EQLKSGTASV VCLLNNFYPR EAKVQWKVDN A LQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL SSPVTKSFNR GEC |
-Macromolecule #3: Circumsporozoite protein
Macromolecule | Name: Circumsporozoite protein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Plasmodium berghei (eukaryote) |
Molecular weight | Theoretical: 36.397008 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EFATMGILPS PGMPALLSLV SLLSVLLMGC VAQQKSIQAQ RNLNELCYNE GNDNKLYHVL NSKNGKIYNR NTVNRLLADA PEGKKNEKK NEKIERNNKL KQPPPPPNPN DPPPPNPNDP PPPNPNDPPP PNPNDPPPPN ANDPPPPNAN DPAPPNANDP A PPNANDPA ...String: EFATMGILPS PGMPALLSLV SLLSVLLMGC VAQQKSIQAQ RNLNELCYNE GNDNKLYHVL NSKNGKIYNR NTVNRLLADA PEGKKNEKK NEKIERNNKL KQPPPPPNPN DPPPPNPNDP PPPNPNDPPP PNPNDPPPPN ANDPPPPNAN DPAPPNANDP A PPNANDPA PPNANDPAPP NANDPPPPNP NDPAPPNAND PPPPNPNDPA PPQGNNNPQP QPRPQPQPQP QPQPQPQPQP QP RPQPQPQ PGGNNNNKNN NNDDSYIPSA EKILEFVKQI RDSITEEWSQ CQVTCGSGIR VRKRKGSNKK AEDLTLEDID TEI CKMDKC SPHHHHHH |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3.0 mg/mL | |||||||||||||||
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Buffer | pH: 8 Component:
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Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 90 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK III |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 2080 / Average electron dose: 42.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |