Well-defined regions of the Plasmodium falciparum reticulocyte binding protein homologue 4 mediate interaction with red blood cell membrane

Jeison García, Hernando Curtidor, Carlos G. Pinzón, Manuel A. Patarroyo, Magnolia Vanegas, Martha Forero, Manuel E. Patarroyo

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Two widely studied parasite protein families are considered attractive targets for developing a fully effective antimalarial vaccine: the erythrocyte binding antigen (EBA) family defining a sialic acid-dependent invasion pathway, and reticulocyte-binding homologue (RH) proteins associated with sialic acid-independent red blood cell (RBC) invasion. In this study, the micronemal invasive PfRH4 protein was finely mapped using 20-mer-long synthetic peptides spanning the entire protein length to identify protein regions that establish high affinity interactions with human RBCs. Twenty conserved, mainly α-helical high-activity binding peptides (HABPs) with nanomolar dissociation constants and recognizing 32, 25, 22, and 20 kDaRBCmembrane molecules in a chymotrypsin and/or trypsin-sensitive manner were identified in this protein. Anti-PfRH4 rabbit sera and PfRH4 HABPs inhibited merozoite invasion in vitro, therefore suggesting the implication of these HABPs in Plasmodium falciparum invasion and supporting their inclusion in further structural and immunological studies to design potential components of a minimal subunit-based, multiantigenic, chemically synthesized antimalarial vaccine.

Original languageEnglish (US)
Pages (from-to)811-821
Number of pages11
JournalJournal of Medicinal Chemistry
Volume53
Issue number2
DOIs
StatePublished - 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Well-defined regions of the Plasmodium falciparum reticulocyte binding protein homologue 4 mediate interaction with red blood cell membrane'. Together they form a unique fingerprint.

Cite this