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- PDB-9zfy: 7160 Fab in complex with Plasmodium falciparum rsCSP -

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Basic information

Entry
Database: PDB / ID: 9zfy
Title7160 Fab in complex with Plasmodium falciparum rsCSP
Components
  • Circumsporozoite Protein
  • Fab 7160 Heavy Chain
  • Fab 7160 Light Chain
KeywordsIMMUNE SYSTEM / Plasmodium / malaria / CSP / Fab / homotypic
Biological speciesHomo sapiens (human)
Plasmodium falciparum (malaria parasite P. falciparum)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å
AuthorsCannac, F. / Lee, W.H. / Ward, A.B.
Funding support United States, 2items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-056202 United States
Bill & Melinda Gates FoundationIINV-004923 United States
CitationJournal: PLoS Pathog / Year: 2026
Title: 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.
History
DepositionDec 2, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 27, 2026Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
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Revision 1.0May 27, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
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Revision 1.1Jun 17, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Revision 1.1Jun 17, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
H: Fab 7160 Light Chain
D: Fab 7160 Light Chain
J: Circumsporozoite Protein
G: Fab 7160 Heavy Chain
C: Fab 7160 Heavy Chain


Theoretical massNumber of molelcules
Total (without water)125,5295
Polymers125,5295
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Antibody Fab 7160 Light Chain


Mass: 24246.094 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
#2: Protein Circumsporozoite Protein


Mass: 30232.156 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum (malaria parasite P. falciparum)
Production host: Escherichia coli (E. coli)
#3: Antibody Fab 7160 Heavy Chain


Mass: 23402.287 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Cricetulus griseus (Chinese hamster)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: 7160 Fab in complex with Plasmodium falciparum rsCSP / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
Source (natural)Organism: Plasmodium falciparum (malaria parasite P. falciparum)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.4
SpecimenConc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K

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Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: LAB6 / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 190000 X / Nominal defocus max: 1600 nm / Nominal defocus min: 600 nm / Cs: 2.7 mm / C2 aperture diameter: 20 µm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 60 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2541

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.21.1_5286model refinement
3EPUimage acquisition
5cryoSPARCCTF correction
10cryoSPARCinitial Euler assignment
11cryoSPARCfinal Euler assignment
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 116764 / Symmetry type: POINT
RefinementHighest resolution: 3.55 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0047016
ELECTRON MICROSCOPYf_angle_d0.6299549
ELECTRON MICROSCOPYf_dihedral_angle_d12.9062533
ELECTRON MICROSCOPYf_chiral_restr0.0461073
ELECTRON MICROSCOPYf_plane_restr0.0051233

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