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- EMDB-27788: Cryo-EM structure of 356 Fab in complex with recombinant shortene... -
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Basic information
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Title | Cryo-EM structure of 356 Fab in complex with recombinant shortened Plasmodium falciparum circumsporozoite protein (rsCSP) | |||||||||
![]() | Cryo-EM structure of 356 Fab in complex with recombinant shortened Plasmodium falciparum circumsporozoite protein (rsCSP) | |||||||||
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![]() | malaria antibody / PfCSP / IMMUNE SYSTEM | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Martin GM / Ward AB | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 37.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.8 KB 17.8 KB | Display Display | ![]() |
Images | ![]() | 163.4 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 37.7 MB 37.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 984.3 KB | Display | ![]() |
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Full document | ![]() | 983.9 KB | Display | |
Data in XML | ![]() | 11.4 KB | Display | |
Data in CIF | ![]() | 13.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dz4MC ![]() 8dytC ![]() 8dywC ![]() 8dyxC ![]() 8dyyC ![]() 8dz3C ![]() 8dz5C ![]() 8ekfC M: atomic model generated by this map C: citing same article ( |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | Cryo-EM structure of 356 Fab in complex with recombinant shortened Plasmodium falciparum circumsporozoite protein (rsCSP) | ||||||||||||||||||||
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 356 Fab in complex with...
File | emd_27788_half_map_1.map | ||||||||||||
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Annotation | Cryo-EM structure of 356 Fab in complex with recombinant shortened Plasmodium falciparum circumsporozoite protein (rsCSP) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Cryo-EM structure of 356 Fab in complex with...
File | emd_27788_half_map_2.map | ||||||||||||
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Annotation | Cryo-EM structure of 356 Fab in complex with recombinant shortened Plasmodium falciparum circumsporozoite protein (rsCSP) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 356 Fab - rsCSP complex
Entire | Name: 356 Fab - rsCSP complex |
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Components |
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-Supramolecule #1: 356 Fab - rsCSP complex
Supramolecule | Name: 356 Fab - rsCSP 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: ![]() ![]() |
-Supramolecule #3: 356 Fab light chain, 356 Fab heavy chain
Supramolecule | Name: 356 Fab light chain, 356 Fab heavy chain / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Circumsporozoite protein
Macromolecule | Name: Circumsporozoite protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 30.232156 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: YGSSSNTRVL NELNYDNAGT NLYNELEMNY YGKQENWYSL KKNSRSLGEN DDGNNEDNEK LRKPKHKKLK QPADGNPDPN ANPNVDPNA NPNVDPNANP NVDPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP N ANPNANPN ...String: YGSSSNTRVL NELNYDNAGT NLYNELEMNY YGKQENWYSL KKNSRSLGEN DDGNNEDNEK LRKPKHKKLK QPADGNPDPN ANPNVDPNA NPNVDPNANP NVDPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP NANPNANPNA NPNANPNANP N ANPNANPN KNNQGNGQGH NMPNDPNRNV DENANANSAV KNNNNEEPSD KHIKEYLNKI QNSLSTEWSP CSVTCGNGIQ VR IKPGSAN KPKDELDYAN DIEKKICKME KCSSVFNVVN S |
-Macromolecule #2: 356 Fab light chain
Macromolecule | Name: 356 Fab light chain / type: protein_or_peptide / ID: 2 / Number of copies: 11 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.165775 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QIVMTQSPAT VSVSPGERAT LSCRASRSVT SKLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYFCQ QYNNGFTFGP GTKVDFKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String: QIVMTQSPAT VSVSPGERAT LSCRASRSVT SKLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYFCQ QYNNGFTFGP GTKVDFKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC |
-Macromolecule #3: 356 Fab heavy chain
Macromolecule | Name: 356 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 11 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.675572 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLVESGGG VVQPGRSLRL SCAASGFTFR NFGMHWVRQT PGKGLEWVAV IWHDGSNKFY ADSVEGRFTI SRDNSKNMIY LQMNSLRVE DTAIYYCARD SLFYDHDNSG YYGYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: QVQLVESGGG VVQPGRSLRL SCAASGFTFR NFGMHWVRQT PGKGLEWVAV IWHDGSNKFY ADSVEGRFTI SRDNSKNMIY LQMNSLRVE DTAIYYCARD SLFYDHDNSG YYGYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS 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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 189641 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |