12FC

Crystal structure of unliganded Fab 7118

12FC の概要

• エントリーDOI: 10.2210/pdb12fc/pdb
• 分子名称: Heavy Chain of Fab 7118, Light Chain of Fab 7188 (3 entities in total)
• 機能のキーワード: antibody for malaria, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48889.84

構造登録者

Jain, M.,Wilson, I.A. (登録日: 2026-04-01, 公開日: 2026-05-27, 最終更新日: 2026-06-17)

主引用文献

Jain, M.,Cannac, F.,Agrawal, S.,Lee, W.H.,Loeffler, J.R.,Fernandez-Quintero, M.L.,Gonzalez-Paez, G.E.,Moskovitz, R.,Ward, A.B.,Wilson, I.A.
Structural basis for conserved and distinct antigen recognition by a lineage of malaria-protective antibodies.
Plos Pathog., 22:e1014243-e1014243, 2026

PubMed Abstract: 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.

PubMed: 42234703
DOI: 10.1371/journal.ppat.1014243

実験手法

X-RAY DIFFRACTION (2.29 Å)