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This Article ACCEPTED PREPRINT Full Text (PDF) All Versions of this Article: ps.035923.108v1 17/10/1719    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pinzon, C. G Articles by Patarroyo, M. E. PubMed PubMed Citation Articles by Pinzon, C. G Articles by Patarroyo, M. E. Social Bookmarking                   What's this?

Identification of Plasmodium falciparum RhopH3 protein peptides that specifically bind to erythrocytes and inhibit merozoite invasion

¹ Fundacion Instituto de Inmunologia de Colombia FIDIC;
² Fundacion Instituto de Inmunologia de Colombia FIDIC branch Universidad del Rosario;
³ Fundacion Instituto de Inmunologia de Colombia FIDIC and Universidad Nacional de Colombia

(RECEIVED April 21, 2008; ACCEPTED June 25, 2008)

The identification of sequences involved in binding to erythrocytes is an important step for understanding the molecular basis of merozoite-erythrocyte interactions that take place during invasion of the Plasmodium falciparum malaria parasite into host cells. Several molecules located in the apical organelles (micronemes, rhoptry, dense granules) of the invasive-stage parasite are essential for erythrocyte recognition, invasion and establishment of the nascent parasitophorous vacuole. Particularly, it has been demonstrated that rhoptry proteins play an important role in binding to erythrocyte surface receptors, amongst which is the PfRhopH3 protein, which triggers important immune responses in patients from endemic regions. It has also been reported that anti-RhopH3 antibodies inhibit in vitro invasion of erythrocytes, further supporting its direct involvement in erythrocytes invasion processes. In this study, PfRhopH3 consecutive peptides were synthesised and tested in erythrocyte binding assays for identifying those regions mediating binding to erythrocytes. Fourteen PfRhopH3 peptides presenting high specific binding activity were found, whose binding were saturable and presented nanomolar dissociation constants. These high activity binding peptides (HABPs) were characterised by having -helical structural elements as determined by CD; and receptors of possible sialic acid-dependent and/or glycoprotein-dependent nature, as evidenced in enzyme-treated erythrocyte binding assays and further corroborated by cross-linking assay results. Furthermore, these HABPs inhibited merozoite in vitro invasion of normal erythrocytes at 200 µM by up to 60% and 90%, suggesting that some RhopH3 protein regions are involved in the P. falciparum erythrocyte invasion.

Keywords: High activity binding peptides; Malaria; Plasmodium falciparum; RhopH3 protein

⁴ E-mail: mepatarr{at}mail.com

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