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Structural modifications to a high-activity binding peptide located within the PfEMP1 NTS domain induce protection against P. falciparum malaria in Aotus monkeys.

Curtidor H, Torres MH, Alba MP, Patarroyo ME
Biol Chem 388 25-36 (2007)
Cited: 7 times
EuropePMC logo PMID: 17214546

Abstract

Binding of P. falciparum-infected erythrocytes to vascular endothelium and to uninfected erythrocytes is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP-1 and various receptors, both on the vascular endothelium and on the erythrocyte surface. Consecutive, non-overlapping peptides spanning the N-terminal segment (NTS) and Duffy-binding-like PfEMP1 sequence alpha-domain (DBLalpha) of this protein were tested in erythrocyte and C32 cell binding assays. Eight peptides specifically bound to C32 cells, and were named high-activity binding peptides (HABPs). No erythrocyte binding HABPs were found in this region. Strikingly, three HABPs [6504 ((1)MVELA KMGPK EAAGG DDIED(20)), 6505 ((21)ESAKH MFDRI GKDVY DKVKE(40)) and 6506 ((41)YRAKE RGKGL QGRLS EAKFEK(60))] are located within the NTS, for which no specific function has yet been described. HABP 6505 is neither immunogenic nor protection-inducing; therefore, based on our previous reports, critical amino acids (shown in bold) in HABP-C32 cell binding were identified and replaced to modify HABP immunogenicity and protectivity. Analogue peptide 12722 (ESAKH KFDRI GKDVY DMVKE) produced high antibody titres and completely protected three out of 12 vaccinated Aotus monkeys and 23410 (KHKFD FIGKI VYDMV KER) also produced high protection-inducing titres and completely protected one out of eight monkeys. (1)H NMR studies showed that all peptides were helical. Binding of these peptides to isolated HLADRbeta1 molecules did not reveal any preference, suggesting that they could bind to molecules not studied here.

Reviews citing this publication (1)

  1. Molecular approaches to field studies of malaria. Beck HP, Tetteh K. Trends Parasitol 24 585-589 (2008)

Articles citing this publication (6)

  1. Research and in situ conservation of owl monkeys enhances environmental law enforcement at the Colombian-Peruvian border. Maldonado AM, Peck MR. Am J Primatol 76 658-669 (2014)
  2. Synthetic peptides from conserved regions of the Plasmodium falciparum early transcribed membrane and ring exported proteins bind specifically to red blood cell proteins. Garcia J, Curtidor H, Obando-Martinez AZ, Vizcaíno C, Pinto M, Martinez NL, Patarroyo MA, Patarroyo ME. Vaccine 27 6877-6886 (2009)
  3. Binding activity, structure, and immunogenicity of synthetic peptides derived from Plasmodium falciparum CelTOS and TRSP proteins. Curtidor H, Arévalo-Pinzón G, Bermudez A, Calderon D, Vanegas M, Patiño LC, Patarroyo MA, Patarroyo ME. Amino Acids 43 365-378 (2012)
  4. High affinity interactions between red blood cell receptors and synthetic Plasmodium thrombospondin-related apical merozoite protein (PTRAMP) peptides. Calderón JC, Curtidor H, González O, Cifuentes G, Reyes C, Patarroyo ME. Biochimie 90 802-810 (2008)
  5. Using the PfEMP1 head structure binding motif to deal a blow at severe malaria. Patarroyo ME, Alba MP, Curtidor H, Vanegas M, Almonacid H, Patarroyo MA. PLoS One 9 e88420 (2014)
  6. A Maurer's cleft-associated Plasmodium falciparum membrane-associated histidine-rich protein peptide specifically interacts with the erythrocyte membrane. García J, Curtidor H, Gil OL, Vanegas M, Patarroyo ME. Biochem Biophys Res Commun 380 122-126 (2009)


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