8GIE

Crystal structure of a designed single-component Plasmodium falciparum AMA1-RON2L insertion fusion immunogen 2

8GIE の概要

• エントリーDOI: 10.2210/pdb8gie/pdb
• 分子名称: Apical membrane antigen 1, rhoptry neck protein 2 chimera (2 entities in total)
• 機能のキーワード: single component immunogens, malaria vaccines, cell invasion
• 由来する生物種: Plasmodium falciparum 3D7; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38587.02

構造登録者

Patel, P.N.,Tolia, N.H. (登録日: 2023-03-14, 公開日: 2023-08-30, 最終更新日: 2024-11-20)

主引用文献

Patel, P.N.,Dickey, T.H.,Diouf, A.,Salinas, N.D.,McAleese, H.,Ouahes, T.,Long, C.A.,Miura, K.,Lambert, L.E.,Tolia, N.H.
Structure-based design of a strain transcending AMA1-RON2L malaria vaccine.
Nat Commun, 14:5345-5345, 2023

PubMed Abstract: Apical membrane antigen 1 (AMA1) is a key malaria vaccine candidate and target of neutralizing antibodies. AMA1 binds to a loop in rhoptry neck protein 2 (RON2L) to form the moving junction during parasite invasion of host cells, and this complex is conserved among apicomplexan parasites. AMA1-RON2L complex immunization achieves higher growth inhibitory activity than AMA1 alone and protects mice against Plasmodium yoelii challenge. Here, three single-component AMA1-RON2L immunogens were designed that retain the structure of the two-component AMA1-RON2L complex: one structure-based design (SBD1) and two insertion fusions. All immunogens elicited high antibody titers with potent growth inhibitory activity, yet these antibodies did not block RON2L binding to AMA1. The SBD1 immunogen induced significantly more potent strain-transcending neutralizing antibody responses against diverse strains of Plasmodium falciparum than AMA1 or AMA1-RON2L complex vaccination. This indicates that SBD1 directs neutralizing antibody responses to strain-transcending epitopes in AMA1 that are independent of RON2L binding. This work underscores the importance of neutralization mechanisms that are distinct from RON2 blockade. The stable single-component SBD1 immunogen elicits potent strain-transcending protection that may drive the development of next-generation vaccines for improved malaria and apicomplexan parasite control.

PubMed: 37660103
DOI: 10.1038/s41467-023-40878-7

実験手法

X-RAY DIFFRACTION (1.85 Å)