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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | 7160 Fab in complex with Plasmodium falciparum rsCSP | |||||||||
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Sample |
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Keywords | Plasmodium / malaria / CSP / Fab / homotypic / IMMUNE SYSTEM | |||||||||
| Biological species | ![]() Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.55 Å | |||||||||
Authors | Cannac F / Lee WH / Ward AB | |||||||||
| Funding support | United States, 2 items
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Citation | Journal: PLoS Pathog / Year: 2026Title: Structural basis for conserved and distinct antigen recognition by a lineage of malaria-protective antibodies. Authors: Monika Jain / Fabien Cannac / Sashank Agrawal / Wen-Hsin Lee / Johannes R Loeffler / Monica L Fernández-Quintero / Gonzalo E González-Páez / Re'em Moskovitz / Andrew B Ward / Ian A Wilson / ![]() Abstract: Monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) have demonstrated substantial promise in preventing malaria infection and disease. PfCSP is ...Monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) have demonstrated substantial promise in preventing malaria infection and disease. PfCSP is characterized by a central region composed of repetitive NANP motifs, which serve as major targets for protective antibodies. Several potent mAbs targeting this region exhibit homotypic Fab-Fab interactions, which enhance antigen binding and contribute to their neutralization potency. Among these, mAb 399, encoded by the IGHV3-49/IGKV2D-29 (VH3-49/VK2D-29) germline lineages, forms head-to-head inter-Fab contacts mediated primarily by germline-encoded residues. Here, we determined X-ray and cryo-EM structures of two additional Fabs, derived from the same germline lineages, 7160 and 7118, in their unliganded forms and with PfCSP-derived peptides or recombinant shortened CSP. Both Fabs bound NANP6 repeats with high affinity (KD 6-10 nM). Fab 7160 formed germline-encoded inter-Fab homotypic interactions resembling Fab 399, indicating a conserved and preconfigured mode of antigen recognition. In contrast, Fab 7118 does not form homotypic contacts and adopts a distinct binding mode, which precludes inter-Fab interactions. These findings highlight the structural versatility of VH3-49/VK2D-29-derived antibodies and demonstrate that their CDR loop variations can modulate antibody conformation, homotypic Fab-Fab interactions, and epitope engagement. Our study further defines this class of germline-encoded anti-CSP antibodies and provides mechanistic insights into how they achieve high-avidity binding and protective immunity either through or independent of pre-configured Fab-Fab interactions with important implications for germline-targeting malaria vaccine design. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_74165.map.gz | 306.6 MB | EMDB map data format | |
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| Header (meta data) | emd-74165-v30.xml emd-74165.xml | 22.9 KB 22.9 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_74165_fsc.xml | 14.6 KB | Display | FSC data file |
| Images | emd_74165.png | 40.3 KB | ||
| Masks | emd_74165_msk_1.map | 325 MB | Mask map | |
| Filedesc metadata | emd-74165.cif.gz | 6.5 KB | ||
| Others | emd_74165_half_map_1.map.gz emd_74165_half_map_2.map.gz | 301.9 MB 301.9 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-74165 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-74165 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9zfyMC ![]() 12fcC ![]() 12fdC ![]() 12feC ![]() 9zfzC ![]() 9zm7C ![]() 9zm8C ![]() 9zm9C ![]() 9zmaC ![]() 9zmbC ![]() 9zmcC M: atomic model generated by this map C: citing same article ( |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_74165.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.718 Å | ||||||||||||||||||||||||||||||||||||
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_74165_msk_1.map | ||||||||||||
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-Half map: #1
| File | emd_74165_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_74165_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : 7160 Fab in complex with Plasmodium falciparum rsCSP
| Entire | Name: 7160 Fab in complex with Plasmodium falciparum rsCSP |
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| Components |
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-Supramolecule #1: 7160 Fab in complex with Plasmodium falciparum rsCSP
| Supramolecule | Name: 7160 Fab in complex with Plasmodium falciparum rsCSP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: ![]() |
-Macromolecule #1: Fab 7160 Light Chain
| Macromolecule | Name: Fab 7160 Light Chain / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 24.246094 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: DIVMTQTPLS LSVTPGQPAS ISCKSSQSLL DNDGKTYLYW YLQKPGQSPQ LVIYEVSNRF SGVPDRFSGS GSGTDFTLKI RRVEAEDVG VYYCMQRIDL PWTFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String: DIVMTQTPLS LSVTPGQPAS ISCKSSQSLL DNDGKTYLYW YLQKPGQSPQ LVIYEVSNRF SGVPDRFSGS GSGTDFTLKI RRVEAEDVG VYYCMQRIDL PWTFGQGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C |
-Macromolecule #2: Circumsporozoite Protein
| Macromolecule | Name: Circumsporozoite Protein / type: protein_or_peptide / ID: 2 / 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 #3: Fab 7160 Heavy Chain
| Macromolecule | Name: Fab 7160 Heavy Chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 23.402287 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: EVQLVESGGG LVQPGRSLRV SCTTSGFTFG DYAMSWFRQA PGKGLEWVGF IRSKGYGGTP EYAASVKGRF TISRDDSKRT AYLQMNSLK TEDTAVYYCT RVGIEVSTAV YWGPGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: EVQLVESGGG LVQPGRSLRV SCTTSGFTFG DYAMSWFRQA PGKGLEWVGF IRSKGYGGTP EYAASVKGRF TISRDDSKRT AYLQMNSLK TEDTAVYYCT RVGIEVSTAV YWGPGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEP |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 1 mg/mL |
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| Buffer | pH: 7.4 |
| Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS GLACIOS |
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| Image recording | Film or detector model: TFS FALCON 4i (4k x 4k) / Number grids imaged: 1 / Number real images: 2541 / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: LAB6 |
| Electron optics | C2 aperture diameter: 20.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 190000 |
| Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
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Keywords
Homo sapiens (human)
Authors
United States, 2 items
Citation











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