Papers by Raul Ternero Herrera
Proceedings of the National Academy of Sciences, 2011
The commitment of Plasmodium merozoites to invade red blood cells (RBCs) is marked by the formati... more The commitment of Plasmodium merozoites to invade red blood cells (RBCs) is marked by the formation of a junction between the merozoite and the RBC and the coordinated induction of the parasitophorous vacuole. Despite its importance, the molecular events underlying the parasite’s commitment to invasion are not well understood. Here we show that the interaction of two parasite proteins, RON2 and AMA1, known to be critical for invasion, is essential to trigger junction formation. Using antibodies (Abs) that bind near the hydrophobic pocket of AMA1 and AMA1 mutated in the pocket, we identified RON2’s binding site on AMA1. Abs specific for the AMA1 pocket blocked junction formation and the induction of the parasitophorous vacuole. We also identified the critical residues in the RON2 peptide (previously shown to bind AMA1) that are required for binding to the AMA1 pocket, namely, two conserved, disulfide-linked cysteines. The RON2 peptide blocked junction formation but, unlike the AMA1-s...
Infection and Immunity, 2013
Apical membrane antigen 1 (AMA1) is a leading vaccine candidate, but the allelic polymorphism is ... more Apical membrane antigen 1 (AMA1) is a leading vaccine candidate, but the allelic polymorphism is a stumbling block for vaccine development. We previously showed that a global set of AMA1 haplotypes could be grouped into six genetic populations. Using this information, six recombinant AMA1 proteins representing each population were produced. Rabbits were immunized with either a single recombinant AMA1 protein or mixtures of recombinant AMA1 proteins (mixtures of 4, 5, or 6 AMA1 proteins). Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), and purified IgG from each rabbit was used for growth inhibition assay (GIA) with 12 different clones of parasites (a total of 108 immunogen-parasite combinations). Levels of antibodies to all six AMA1 proteins were similar when the antibodies were tested against homologous antigens. When the percent inhibitions in GIA were plotted against the number of ELISA units measured with homologous AMA1, all data points followed a si...
Eukaryotic Cell, 2012
Thrombospondin repeat (TSR)-like domains are structures involved with cell adhesion. Plasmodium f... more Thrombospondin repeat (TSR)-like domains are structures involved with cell adhesion. Plasmodium falciparum proteins containing TSR domains play crucial roles in parasite development. In particular, the preerythrocytic P. falciparum circumsporozoite protein is involved in hepatocyte invasion. The importance of these domains in two other malaria proteins, the merozoite-specific thrombospondin-related anonymous protein (MTRAP) and the thrombospondin-related apical membrane protein (PTRAMP), were assessed using near-full-length recombinant proteins composed of the extracellular domains produced in Escherichia coli . MTRAP is thought to be released from invasive organelles identified as micronemes during merozoite invasion to mediate motility and host cell invasion through an interaction with aldolase, an actin binding protein involved in the moving junction. PTRAMP function remains unknown. In this study, the conformation of recombinant MTRAP (rMTRAP) appeared to be a highly extended pr...
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Papers by Raul Ternero Herrera