ArticlePloS one2015
Crystal structure of Plasmodium knowlesi apical membrane antigen 1 and its complex with an invasion-inhibitory monoclonal antibody.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages.Nature communications · 2024Article
- Conformational variability in the D2 loop ofJournal of structural biology: X · 2024Article
- Review
- Defining species-specific and conserved interactions of apical membrane protein 1 during erythrocyte invasion in malaria to inform multi-species vaccines.Cellular and molecular life sciences : CMLS · 2023Article
- The Impact of Geographical Variation inTropical medicine and infectious disease · 2023Article
- Antibodies Against theFrontiers in cellular and infection microbiology · 2021Article
- Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi.PLoS neglected tropical diseases · 2020Article
- Article
- Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites.Scientific reports · 2018Article
- Proteome-wide mapping of immune features onto Plasmodium protein three-dimensional structures.Scientific reports · 2018Article
- Review
- Heterologous expression ofPeerJ · 2017Article
- Article
- Immunization with the Malaria Diversity-Covering Blood-Stage Vaccine CandidateFrontiers in immunology · 2017Article
- Stability of the Plasmodium falciparum AMA1-RON2 Complex Is Governed by the Domain II (DII) Loop.PloS one · 2016Article
- Low levels of polymorphisms and no evidence for diversifying selection on the Plasmodium knowlesi Apical Membrane Antigen 1 gene.PloS one · 2015Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host's humoral response to AMA1.
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