7lr3
From Proteopedia
Complex of Fab 2/6.14 with domain 3 of P. berghei HAP2
Structural highlights
FunctionHAP2_PLABA During fertilization, required on male gametes for their fusion with female gametes, and for subsequent ookinete formation in the host (PubMed:18403203, PubMed:18367645, PubMed:21209845, PubMed:29212032). Thereby, required for mosquito-mediated transmission to other animals (PubMed:18403203, PubMed:18367645, PubMed:29212032). Probably initiates the fusion of gamete cell membranes by inserting part of its extracellular domain into the cell membrane of a female gamete (PubMed:20080406).[1] [2] [3] [4] [5] Publication Abstract from PubMedHAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in Plasmodium 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 Plasmodium berghei HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of Plasmodium berghei 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 Plasmodium D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission. Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2.,Feng J, Dong X, DeCosta A, Su Y, Angrisano F, Sala KA, Blagborough AM, Lu C, Springer TA Elife. 2021 Dec 23;10:e74707. doi: 10.7554/eLife.74707. PMID:34939934[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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