Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis for conserved and distinct antigen recognition by a lineage of malaria-protective antibodies.
Journal, issue, pages	PLoS Pathog, Vol. 22, Issue 6, Page e1014243, Year 2026
Publish date	Jun 3, 2026
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 /
PubMed 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.
External links	PLoS Pathog / PubMed:42234703 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.88 - 3.55 Å
Structure data	74165 9zfy EMDB-74165, PDB-9zfy: 7160 Fab in complex with Plasmodium falciparum rsCSP Method: EM (single particle) / Resolution: 3.55 Å 74167 9zfz EMDB-74167, PDB-9zfz: 7118 Fab in complex with Plasmodium falciparum rsCSP Method: EM (single particle) / Resolution: 3.3 Å PDB-12fc: Crystal structure of unliganded Fab 7118 Method: X-RAY DIFFRACTION / Resolution: 2.29 Å PDB-12fd: Crystal structure of unliganded Fab 7160 Method: X-RAY DIFFRACTION / Resolution: 2.39 Å PDB-12fe: Crystal structure of unliganded Fab 399 Method: X-RAY DIFFRACTION / Resolution: 2.29 Å PDB-9zm7: Crystal structure of Fab 7160 in complex with junctional region from circumsporozoite protein Method: X-RAY DIFFRACTION / Resolution: 2.3 Å PDB-9zm8: Crystal structure of 7160 in complex with minor repeat region from circumsporozoite protein Method: X-RAY DIFFRACTION / Resolution: 2.27 Å PDB-9zm9: Crystal structure of Fab 7160 in complex with short major repeat region (NPNA3) from circumsporozoite protein Method: X-RAY DIFFRACTION / Resolution: 1.88 Å PDB-9zma: Crystal structure of Fab 7160 in complex with major repeat region (NANP6)from circumsporozoite protein Method: X-RAY DIFFRACTION / Resolution: 2.33 Å PDB-9zmb: Crystal structure of Fab 7118 in complex with minor repeat region from circumsporozoite protein Method: X-RAY DIFFRACTION / Resolution: 2.09 Å PDB-9zmc: Crystal structure of Fab 7118 in complex with major repeat region (NANP6) from circumsporozoite protein Method: X-RAY DIFFRACTION / Resolution: 2 Å
Chemicals	ChemComp-HOH: WATER
Source	plasmodium falciparum (malaria parasite P. falciparum) homo sapiens (human) plasmodium falciparum 3d7 (eukaryote)
Keywords	IMMUNE SYSTEM / Antibody for Malaria / Antibody / Malaria / Plasmodium / CSP / Fab / homotypic