Binding ofPlasmodiummerozoite proteins RON2 and AMA1 triggers commitment to invasion

• DOI: 10.1073/pnas.1110303108
• Publication Date: 2011-07-26T04:02:29Z
• Authors: Prakash Srinivasan; Wandy L. Beatty; Ababacar Diouf; Raul Herrera; Xavier Ambroggio; J. Kathleen Moch; Jessica S. Tyler; David L. Narum; Susan K. Pierce; John C. Boothroyd; J. David Haynes; Louis H. Miller
• Keywords: 0301 basic medicine; Binding Sites; Cytochalasin D; Erythrocytes; Merozoites; Molecular Sequence Data; Plasmodium falciparum; Protozoan Proteins; Antibodies, Protozoan; Models, Biological; 3. Good health; Protein Transport; Structure-Activity Relationship; 03 medical and health sciences; Fructose-Bisphosphate Aldolase; Animals; Amino Acid Sequence; Cysteine; Hydrophobic and Hydrophilic Interactions; Conserved Sequence; Protein Binding

The commitment of Plasmodium merozoites to invade red blood cells (RBCs) is marked by the formation a junction between merozoite and RBC coordinated induction parasitophorous vacuole. Despite its importance, molecular events underlying parasite’s invasion are not well understood. Here we show that interaction two parasite proteins, RON2 AMA1, known be critical for invasion, essential trigger formation. Using antibodies (Abs) bind near hydrophobic pocket AMA1 mutated in pocket, identified RON2’s binding site on AMA1. Abs specific blocked We also residues peptide (previously shown AMA1) required namely, conserved, disulfide-linked cysteines. but, unlike AMA1-specific Ab, did block vacuole, indicating vacuole molecularly distinct steps process. Collectively, these results identify as step commits point potential vaccine candidate.