+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-27781 | |||||||||
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Title | Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide | |||||||||
Map data | Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide | |||||||||
Sample |
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Keywords | malaria antibody / PfCSP / IMMUNE SYSTEM | |||||||||
Function / homology | Function and homology information | |||||||||
Biological species | Plasmodium falciparum (malaria parasite P. falciparum) / Homo sapiens (human) / Plasmodium falciparum 3D7 (eukaryote) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Martin GM / Ward AB | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection. Authors: Gregory M Martin / Jonathan L Torres / Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Grace Gibson / Re'em Moskovitz / Nathan Beutler / Diana D Jung / Jeffrey Copps / Wen-Hsin Lee ...Authors: Gregory M Martin / Jonathan L Torres / Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Grace Gibson / Re'em Moskovitz / Nathan Beutler / Diana D Jung / Jeffrey Copps / Wen-Hsin Lee / Gonzalo Gonzalez-Paez / Daniel Emerling / Randall S MacGill / Emily Locke / C Richter King / Fidel Zavala / Ian A Wilson / Andrew B Ward / Abstract: The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an ...The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3-33 antibodies and highlight key features underlying the potent protection of this antibody family. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_27781.map.gz | 37.9 MB | EMDB map data format | |
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Header (meta data) | emd-27781-v30.xml emd-27781.xml | 17.7 KB 17.7 KB | Display Display | EMDB header |
Images | emd_27781.png | 81.8 KB | ||
Filedesc metadata | emd-27781.cif.gz | 5.8 KB | ||
Others | emd_27781_half_map_1.map.gz emd_27781_half_map_2.map.gz | 37.5 MB 37.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-27781 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-27781 | HTTPS FTP |
-Validation report
Summary document | emd_27781_validation.pdf.gz | 864.2 KB | Display | EMDB validaton report |
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Full document | emd_27781_full_validation.pdf.gz | 863.8 KB | Display | |
Data in XML | emd_27781_validation.xml.gz | 11.4 KB | Display | |
Data in CIF | emd_27781_validation.cif.gz | 13.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27781 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-27781 | HTTPS FTP |
-Related structure data
Related structure data | 8dytMC 8dywC 8dyxC 8dyyC 8dz3C 8dz4C 8dz5C 8ekfC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_27781.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide
File | emd_27781_half_map_1.map | ||||||||||||
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Annotation | Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide
File | emd_27781_half_map_2.map | ||||||||||||
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Annotation | Cryo-EM structure of 227 Fab in complex with (NPNA)8 peptide | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : 227 Fab - (NPNA)8 complex
Entire | Name: 227 Fab - (NPNA)8 complex |
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Components |
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-Supramolecule #1: 227 Fab - (NPNA)8 complex
Supramolecule | Name: 227 Fab - (NPNA)8 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Circumsporozoite protein
Supramolecule | Name: Circumsporozoite protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Plasmodium falciparum (malaria parasite P. falciparum) |
-Supramolecule #3: 227 Fab light chain, 227 Fab heavy chain
Supramolecule | Name: 227 Fab light chain, 227 Fab heavy chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Circumsporozoite protein
Macromolecule | Name: Circumsporozoite protein / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Plasmodium falciparum 3D7 (eukaryote) |
Molecular weight | Theoretical: 3.1892 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: NPNANPNANP NANPNANPNA NPNANPNANP NA UniProtKB: Circumsporozoite protein |
-Macromolecule #2: 227 Fab light chain
Macromolecule | Name: 227 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.859256 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QSVLTQPPSV SGAPGQRVTI SCTGSSSNIG AGYDVHWYQQ LPGTAPKLLI YGNGNRPSGV PDRFSGSKSG TSVSLAITGL QAEDEADYY CQSYDSSLSA FVFGTGTKVT VLGQPKANPT VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADGSP V KAGVETTK ...String: QSVLTQPPSV SGAPGQRVTI SCTGSSSNIG AGYDVHWYQQ LPGTAPKLLI YGNGNRPSGV PDRFSGSKSG TSVSLAITGL QAEDEADYY CQSYDSSLSA FVFGTGTKVT VLGQPKANPT VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADGSP V KAGVETTK PSKQSNNKYA ASSYLSLTPE QWKSHRSYSC QVTHEGSTVE KTVAPTECS |
-Macromolecule #3: 227 Fab heavy chain
Macromolecule | Name: 227 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 49.904219 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLVQSGGG VVQPGRSLRL SCVTSGFTFP AFGMHWVRQA PGKGLEWVAV IWYDGSKKYY ADSVRGRFTI SRDNSRNTLY LQMHSLRAE DTAVYYCARV KNYESSGYSQ CLDYWGQGVL VTVASASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: QVQLVQSGGG VVQPGRSLRL SCVTSGFTFP AFGMHWVRQA PGKGLEWVAV IWYDGSKKYY ADSVRGRFTI SRDNSRNTLY LQMHSLRAE DTAVYYCARV KNYESSGYSQ CLDYWGQGVL VTVASASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTHTCPPCPA PE LLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDW LNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSRDELT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKT TPPVL DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPG |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TECNAI ARCTICA |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 70120 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |