scholarly journals Plasmodium falciparum AMA1 Binds a Rhoptry Neck Protein Homologous to TgRON4, a Component of the Moving Junction in Toxoplasma gondii

2006 ◽  
Vol 5 (7) ◽  
pp. 1169-1173 ◽  
Author(s):  
David L. Alexander ◽  
Shirin Arastu-Kapur ◽  
Jean-Francois Dubremetz ◽  
John C. Boothroyd
Keyword(s):  
Plasmodium Falciparum ◽  
Toxoplasma Gondii ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Rhoptry Neck Protein

ABSTRACT Plasmodium falciparum apical membrane antigen 1 (PfAMA1) coimmunoprecipitates with the Plasmodium homologue of TgRON4, a secreted rhoptry neck protein of Toxoplasma gondii that migrates at the moving junction in association with TgAMA1 during invasion. PfRON4 also originates in the rhoptry necks, suggesting that this unusual collaboration of micronemes and rhoptries is a conserved feature of Apicomplexa.

Development of Inhibitors of Plasmodium falciparum Apical Membrane Antigen 1 Based on Fragment Screening

2013 ◽  
Vol 66 (12) ◽  
pp. 1530 ◽  
Author(s):  
San Sui Lim ◽  
Cael O. Debono ◽  
Christopher A. MacRaild ◽  
Indu R. Chandrashekaran ◽  
Olan Dolezal ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Apical Membrane ◽  
Strain Specificity ◽  
Apical Membrane Antigen 1 ◽  
Fragment Screening ◽  
Hit Rate ◽  
Apical Membrane Antigen ◽  
Human Red Blood Cells ◽  
Hydrophobic Cleft ◽  
Rhoptry Neck Protein

Apical membrane antigen 1 (AMA1) is an essential component of the moving junction complex used by Plasmodium falciparum to invade human red blood cells. AMA1 has a conserved hydrophobic cleft that is the site of key interactions with the rhoptry neck protein complex. Our goal is to develop small molecule inhibitors of AMA1 with broad strain specificity, which we are pursuing using a fragment-based approach. In our screening campaign, we identified fragments that bind to the hydrophobic cleft with a hit rate of 5 %. The high hit rate observed strongly suggests that a druggable pocket is present within the cleft.

scholarly journals The Most Polymorphic Residue on Plasmodium falciparum Apical Membrane Antigen 1 Determines Binding of an Invasion-Inhibitory Antibody

2006 ◽  
Vol 74 (5) ◽  
pp. 2628-2636 ◽  
Author(s):  
A. M. Coley ◽  
K. Parisi ◽  
R. Masciantonio ◽  
J. Hoeck ◽  
J. L. Casey ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Apical Membrane ◽  
Site Directed Mutagenesis ◽  
Supporting Evidence ◽  
Inhibitory Antibody ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Immune Pressure ◽  
Polymorphic Residue

ABSTRACT Apical membrane antigen 1 (AMA1) is currently one of the leading malarial vaccine candidates. Anti-AMA1 antibodies can inhibit the invasion of erythrocytes by Plasmodium merozoites and prevent the multiplication of blood-stage parasites. Here we describe an anti-AMA1 monoclonal antibody (MAb 1F9) that inhibits the invasion of Plasmodium falciparum parasites in vitro. We show that both reactivity of MAb 1F9 with AMA1 and MAb 1F9-mediated invasion inhibition were strain specific. Site-directed mutagenesis of a fragment of AMA1 displayed on M13 bacteriophage identified a single polymorphic residue in domain I of AMA1 that is critical for MAb 1F9 binding. The identities of all other polymorphic residues investigated in this domain had little effect on the binding of the antibody. Examination of the P. falciparum AMA1 crystal structure localized this residue to a surface-exposed α-helix at the apex of the polypeptide. This description of a polymorphic inhibitory epitope on AMA1 adds supporting evidence to the hypothesis that immune pressure is responsible for the polymorphisms seen in this molecule.

Plasmodium falciparum: Genetic polymorphism in apical membrane antigen-1 gene from Indian isolates

2008 ◽  
Vol 119 (1) ◽  
pp. 144-151 ◽  
Author(s):  
Vidya Rajesh ◽  
Vijay Kumar Singamsetti ◽  
S. Vidya ◽  
M. Gowrishankar ◽  
M. Elamaran ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Polymorphism ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Indian Isolates

Polymorphism in the gene encoding the apical membrane antigen-1 (AMA-1) of Plasmodium falciparum. X. Asembo Bay Cohort Project

2001 ◽  
Vol 113 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Ananias A. Escalante ◽  
Heather M. Grebert ◽  
Sansanee C. Chaiyaroj ◽  
Magda Magris ◽  
Sukla Biswas ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Apical Membrane ◽  
Gene Encoding ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen
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