9BJG
Crystal structure of broadly neutralizing human monoclonal antibody 75B10 in complex with AMA1
Summary for 9BJG
| Entry DOI | 10.2210/pdb9bjg/pdb |
| Descriptor | Apical membrane antigen 1, 75B10 Fab Heavy Chain, 75B10 Fab Light Chain, ... (4 entities in total) |
| Functional Keywords | apical membrane antigen 1, plasmodium, malaria, antigen-antibody complex, structural protein |
| Biological source | Plasmodium falciparum 3D7 More |
| Total number of polymer chains | 3 |
| Total formula weight | 89967.59 |
| Authors | Patel, P.N.,Tang, W.K.,Tolia, N.H. (deposition date: 2024-04-25, release date: 2025-03-12, Last modification date: 2025-04-02) |
| Primary citation | Patel, P.N.,Diouf, A.,Dickey, T.H.,Tang, W.K.,Hopp, C.S.,Traore, B.,Long, C.A.,Miura, K.,Crompton, P.D.,Tolia, N.H. A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade. Cell Rep Med, 6:101985-101985, 2025 Cited by PubMed Abstract: Plasmodium falciparum apical membrane antigen 1 (AMA1) binds a loop in rhoptry neck protein 2 (RON2L) during red cell invasion and is a target for vaccines and therapeutic antibodies against malaria. Here, we report a panel of AMA1-specific naturally acquired human monoclonal antibodies (hmAbs) derived from individuals living in malaria-endemic regions. Two neutralizing hmAbs engage AMA1 independent of the RON2L-binding site. The hmAb 75B10 demonstrates potent strain-transcending neutralization that is independent of RON2L blockade, emphasizing that epitopes outside the RON2L-binding site elicit broad protection against variant parasite strains. The combination of these hmAbs synergistically enhances parasite neutralization. Vaccination with a structure-based design (SBD1) that mimics the AMA1-RON2L complex elicited antibodies similar to the two neutralizing hmAbs connecting vaccination to naturally acquired immunity in humans. The structural definition of a strain-transcending epitope on AMA1 targeted by naturally acquired hmAb establishes paradigms for developing AMA1-based vaccines and therapeutic antibodies. PubMed: 40020675DOI: 10.1016/j.xcrm.2025.101985 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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