7LR3

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

Summary for 7LR3

• Entry DOI: 10.2210/pdb7lr3/pdb
• Descriptor: D3_2/6.14 Fab light chain, D3_2/6.14 Fab heavy chain, Hapless 2, ... (7 entities in total)
• Functional Keywords: transmission-blocking malaria vaccine, membrane fusion, gamete fusogen, monoclonal antibody, surfactant protein, surfactant protein-immune system complex, surfactant protein/immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 124454.88

Authors

Feng, J.,Dong, X.C.,Lu, C.F.,Springer, T.A. (deposition date: 2021-02-15, release date: 2021-12-15, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)