An Inhibitory Antibody Blocks Interactions between Components of the Malarial Invasion Machinery

@article{Collins2009AnIA,
  title={An Inhibitory Antibody Blocks Interactions between Components of the Malarial Invasion Machinery},
  author={Christine R. Collins and Chrislaine Withers-Martinez and Fiona Hackett and Michael J. Blackman},
  journal={PLoS Pathogens},
  year={2009},
  volume={5}
}
Host cell invasion by apicomplexan pathogens such as the malaria parasite Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from secretory organelles called micronemes and rhoptries. In Toxoplasma a protein complex comprising the microneme apical membrane antigen 1 (AMA1), two rhoptry neck proteins, and a protein called Ts4705, localises to the moving junction, a region of close apposition between parasite and host cell during invasion. Antibodies against AMA1 prevent… 
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169 Citations

Apical membrane antigen 1 as an anti-malarial drug target.
TLDR
The structural details and functional significance of interactions at the hydrophobic cleft of AMA1 are reviewed, and it is argued that this feature of the protein represents an excellent target for the development of drugs that would block host cell invasion by malarial parasites.
Interaction between Plasmodium falciparum Apical Membrane Antigen 1 and the Rhoptry Neck Protein Complex Defines a Key Step in the Erythrocyte Invasion Process of Malaria Parasites*
TLDR
It is proposed that the formation of the AMA1-RON complex is essential for secretion of the rhoptry contents, which then allows the establishment of parasite infection within the parasitophorous vacuole.
Structural and Functional Insights into the Malaria Parasite Moving Junction Complex
TLDR
The crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2 is determined, highlighting clear specificities of the P. falcIParum RON2-AMA1 interaction and suggesting novel approaches to antimalarial therapeutics.
Plasmodium falciparum: genetic and immunogenic characterisation of the rhoptry neck protein PfRON4.
Cross-reactivity between apical membrane antgen 1 and rhoptry neck protein 2 in P. vivax and P. falciparum: A structural and binding study
TLDR
Crystal structure of the complex formed between AMA1 from P. vivax RON2 and a peptide derived from the externally exposed region of P. falciparum AMA1 and PvRON2sp1 is described, underlining its importance in the Plasmodium life cycle and as a target for therapeutic strategies.
Plasmodium falciparum rhoptry neck protein 5 peptides bind to human red blood cells and inhibit parasite invasion
Host Cell Invasion by Apicomplexan Parasites: Insights from the Co-Structure of AMA1 with a RON2 Peptide
TLDR
The structure of TgAMA1 complexed with a RON2 peptide at 1.95 angstrom resolution is determined, providing insights into host cell invasion by apicomplexan parasites.
Plasticity and redundancy among AMA-RON pairs ensure host cell entry of Toxoplasma parasites.
TLDR
It is shown that AMA1, a vaccine candidate, interacts with RON2 to maintain the MJ structural integrity in T. gondii and is subsequently required for parasite internalization.
The RON2-AMA1 Interaction is a Critical Step in Moving Junction-Dependent Invasion by Apicomplexan Parasites
TLDR
This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites, and an intra-species conservation of their interaction.
Novel malaria parasite proteins involved in erythrocyte invasion
TLDR
The aim of this project was to uncover novel proteins with a role in invasion by the human malaria parasite Plasmodium falciparum merozoites, with a focus on one protein, the type IV Hsp40, PF11_0443, which contains two TM domains and is expressed during schizogony.
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