7LR3

Complex of Fab 2/6.14 with domain 3 of P. berghei HAP2

7LR3 の概要

• エントリーDOI: 10.2210/pdb7lr3/pdb
• 分子名称: D3_2/6.14 Fab light chain, D3_2/6.14 Fab heavy chain, Hapless 2, ... (7 entities in total)
• 機能のキーワード: transmission-blocking malaria vaccine, membrane fusion, gamete fusogen, monoclonal antibody, surfactant protein, surfactant protein-immune system complex, surfactant protein/immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 124454.88

構造登録者

Feng, J.,Dong, X.C.,Lu, C.F.,Springer, T.A. (登録日: 2021-02-15, 公開日: 2021-12-15, 最終更新日: 2024-11-06)

主引用文献

Feng, J.,Dong, X.,DeCosta, A.,Su, Y.,Angrisano, F.,Sala, K.A.,Blagborough, A.M.,Lu, C.,Springer, T.A.
Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2.
Elife, 10:-, 2021

PubMed Abstract: HAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in have suggested that HAP2 is an attractive target for vaccines that block transmission of malaria. HAP2 has three extracellular domains, arranged in the order D2, D1, and D3. Here, we report monoclonal antibodies against the D3 fragment of HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of in vitro and transmission of malaria in mosquitoes. We also show how this Fab binds the complete HAP2 ectodomain with electron microscopy. The two antibodies cross-react with HAP2 among multiple plasmodial species. Our characterization of the D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission.

PubMed: 34939934
DOI: 10.7554/eLife.74707

実験手法

X-RAY DIFFRACTION (2.8 Å)