Structural modifications to a high-activity binding peptide located within the PfEMP1 NTS domain induce protection against P. falciparum malaria in Aotus monkeys
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Hernando Curtidor
, Mary Helena Torres , Martha Patricia Alba and Manuel E. Patarroyo
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 α-domain (DBLα) 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 (1MVELA KMGPK EAAGG DDIED20), 6505 (21ESAKH MFDRI GKDVY DKVKE40) and 6506 (41YRAKE RGKGL QGRLS EAKFEK60)] 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. 1H NMR studies showed that all peptides were helical. Binding of these peptides to isolated HLADRβ1 molecules did not reveal any preference, suggesting that they could bind to molecules not studied here.
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Articles in the same Issue
- Accumulation of viroid-specific small RNAs and increase in nucleolytic activities linked to viroid-caused pathogenesis
- Characterisation of Plasmodium falciparum RESA-like protein peptides that bind specifically to erythrocytes and inhibit invasion
- Structural modifications to a high-activity binding peptide located within the PfEMP1 NTS domain induce protection against P. falciparum malaria in Aotus monkeys
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Articles in the same Issue
- Accumulation of viroid-specific small RNAs and increase in nucleolytic activities linked to viroid-caused pathogenesis
- Characterisation of Plasmodium falciparum RESA-like protein peptides that bind specifically to erythrocytes and inhibit invasion
- Structural modifications to a high-activity binding peptide located within the PfEMP1 NTS domain induce protection against P. falciparum malaria in Aotus monkeys
- Characterisation of YtfM, a second member of the Omp85 family in Escherichia coli
- Presence of the propeptide on recombinant lysosomal dipeptidase controls both activation and dimerization
- Conformational studies on Arabidopsis sulfurtransferase AtStr1 with spectroscopic methods
- Glycine-assisted enhancement of 1,4-β-d-xylan xylanohydrolase activity at alkaline pH with a pH optimum shift
- Asef is a Cdc42-specific guanine nucleotide exchange factor
- Metal-binding sites at the active site of restriction endonuclease BamHI can conform to a one-ion mechanism
- Interaction of the cellular prion protein with raft-like lipid membranes
- Tissue-specific transcription factor HNF4α inhibits cell proliferation and induces apoptosis in the pancreatic INS-1 β-cell line
- Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis
- The insect metalloproteinase inhibitor gene of the lepidopteran Galleria mellonella encodes two distinct inhibitors
- Activation profiles of the zymogen of aspergilloglutamic peptidase