Plasmodium falciparum EBA-175 kDa protein peptides which bind to human red blood cells

Parasitology ◽  
2000 ◽  
Vol 120 (3) ◽  
pp. 225-235 ◽  
Author(s):  
L. E. RODRIGUEZ ◽  
M. URQUIZA ◽  
M. OCAMPO ◽  
J. SUAREZ ◽  
H. CURTIDOR ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Binding Activity ◽  
Ligand Interaction ◽  
Merozoite Invasion ◽  
Human Red Blood Cells ◽  
Affinity Constants ◽  
Region I ◽  
Binding Peptides ◽  
V Region ◽  
Region Ii

Solid experimental evidence indicates that EBA-175 is used as a ligand by the Plasmodium falciparum merozoite to bind to human RBC, via different binding processing fragments. Using synthetic peptides and specific receptor-ligand interaction methodology, we have identified 6 high-activity binding sequences from the EBA-175 CAMP strain; peptide 1758 (KSYGTPDNIDKNMSLIHKHN), located in the so-called region I for which no binding activity has been reported before, peptides 1779 (NIDRIYDKNLLMIKEHILAI) and 1783 (HRNKKNDKLYRDEWWKVIKK), located in region II, in a sub-region known as 5′ Cys F2, previously reported as being a binding region, and peptides 1814 (DRNSNTLHLKDYRNEENERH), 1815 (YTNQNINISQERDLQKHGFH) and 1818 (NNNFNNIPSRYNLYDKKLDL), in region III–V where antibodies inhibit merozoite invasion of erythrocytes. The affinity constants were between 60 and 180 nM and the critical amino acids involved in the binding were identified. The binding of these peptides to enzyme-treated RBC was analysed; binding of peptide 1814, located in the III–V region, was found to be sialic acid dependent. Some of these high binding peptides were able to inhibit in vitro merozoite invasion and to block the binding of recombinant RII-EBA to RBC. Several of these peptides are located in regions recognized by protective immune clusters of merozoites (ICMs) eluted antibodies.

Fine mapping of Plasmodium falciparum ribosomal phosphoprotein PfP0 revealed sequences with highly specific binding activity to human red blood cells

2009 ◽  
Vol 88 (1) ◽  
pp. 61-74 ◽  
Author(s):  
Gabriela Arevalo-Pinzon ◽  
Hernando Curtidor ◽  
Claudia Reyes ◽  
Martha Pinto ◽  
Carolina Vizcaíno ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Fine Mapping ◽  
Blood Cells ◽  
Specific Binding ◽  
Binding Activity ◽  
Human Red Blood Cells

scholarly journals Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.

1989 ◽  
Vol 169 (4) ◽  
pp. 1309-1321 ◽  
Author(s):  
P A Burke ◽  
S Hirschfeld ◽  
Y Shirayoshi ◽  
J W Kasik ◽  
K Hamada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mhc Class I ◽  
Regulatory Element ◽  
Binding Activity ◽  
Class I ◽  
Specific Expression ◽  
Enhancer Activity ◽  
Region I ◽  
Region Ii ◽  
I Gene

Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor-binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE.

Two MSA 2 peptides that bind to human red blood cells are relevant to Plasmodium falciparum merozoite invasion

2000 ◽  
Vol 55 (3) ◽  
pp. 216-223 ◽  
Author(s):  
M. Ocampo ◽  
M. Urquiza ◽  
F. Guzmán ◽  
L.E. Rodriguez ◽  
J. Suarez ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Merozoite Invasion ◽  
Human Red Blood Cells ◽  
Falciparum Merozoite

scholarly journals Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers.

1993 ◽  
Vol 13 (10) ◽  
pp. 6157-6169 ◽  
Author(s):  
J H Segars ◽  
T Nagata ◽  
V Bours ◽  
J A Medin ◽  
G Franzoso ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mhc Class I ◽  
Binding Activity ◽  
Class I ◽  
Nf Kappa B ◽  
Histocompatibility Complex ◽  
Region I ◽  
Nt2 Cells ◽  
Region Ii ◽  
Receptor Beta

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

scholarly journals Analysis of Human Antibodies to Erythrocyte Binding Antigen 175 of Plasmodium falciparum

2000 ◽  
Vol 68 (10) ◽  
pp. 5559-5566 ◽  
Author(s):  
Daniel M. N. Okenu ◽  
Eleanor M. Riley ◽  
Quentin D. Bickle ◽  
Philip U. Agomo ◽  
Arnoldo Barbosa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Recombinant Proteins ◽  
Large Population ◽  
Clinical Malaria ◽  
Ligand Interaction ◽  
Human Antibodies ◽  
Multistep Process ◽  
Erythrocyte Binding ◽  
Igg3 Subclass ◽  
Region Ii

ABSTRACT Invasion of human erythrocytes by Plasmodium falciparummerozoites is a multistep process. For many strains of the parasite, part of this process requires that the erythrocyte binding antigen 175 (EBA-175) of the merozoite binds to sialic acid residues of glycophorin A on the erythrocyte surface, a receptor-ligand interaction which represents a potential target for inhibition by antibodies. This study characterizes the reactivity of naturally acquired human antibodies with four recombinant proteins representing parts of EBA-175 (region II, regions III to V, and the dimorphic C and F segment region) in populations in which the organism is endemic. Serum immunoglobulin G (IgG) recognizing the recombinant proteins is predominantly of the IgG1 and IgG3 subclasses, and its prevalence increases with age. In a large population study in The Gambia, serum positivity for IgG or IgG1 and IgG3 subclass antibodies to each of the EBA-175 recombinant antigens was not significantly associated with subsequent protection from clinical malaria. However, there was a trend indicating that individuals with high levels of IgG to region II may have some protection.

Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers

1993 ◽  
Vol 13 (10) ◽  
pp. 6157-6169
Author(s):  
J H Segars ◽  
T Nagata ◽  
V Bours ◽  
J A Medin ◽  
G Franzoso ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mhc Class I ◽  
Binding Activity ◽  
Class I ◽  
Nf Kappa B ◽  
Histocompatibility Complex ◽  
Region I ◽  
Nt2 Cells ◽  
Region Ii ◽  
Receptor Beta

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2555-2562 ◽  
Author(s):  
Mark Loyevsky ◽  
Timothy LaVaute ◽  
Charles R. Allerson ◽  
Robert Stearman ◽  
Olakunle O. Kassim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Regulatory Protein ◽  
Protein S ◽  
Fold Increase ◽  
Binding Activity ◽  
Mobility Shift ◽  
Iron Responsive Element ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Electrophoretic Mobility Shift Assays

Abstract This study cloned and sequenced the complementary DNA (cDNA) encoding of a putative malarial iron responsive element-binding protein (PfIRPa) and confirmed its identity to the previously identified iron-regulatory protein (IRP)–like cDNA from Plasmodium falciparum. Sequence alignment showed that the plasmodial sequence has 47% identity with human IRP1. Hemoglobin-free lysates obtained from erythrocyte-stage P falciparum contain a protein that binds a consensus mammalian iron-responsive element (IRE), indicating that a protein(s) with iron-regulatory activity was present in the lysates. IRE-binding activity was found to be iron regulated in the electrophoretic mobility shift assays. Western blot analysis showed a 2-fold increase in the level of PfIRPa in the desferrioxamine-treated cultures versus control or iron-supplemented cells. Malarial IRP was detected by anti-PfIRPa antibody in the IRE-protein complex fromP falciparum lysates. Immunofluorescence studies confirmed the presence of PfIRPa in the infected red blood cells. These findings demonstrate that erythrocyte P falciparum contains an iron-regulated IRP that binds a mammalian consensus IRE sequence, raising the possibility that the malaria parasite expresses transcripts that contain IREs and are iron-dependently regulated.

scholarly journals The Central Role of cAMP in Regulating Plasmodium falciparum Merozoite Invasion of Human Erythrocytes

2014 ◽  
Vol 10 (12) ◽  
pp. e1004520 ◽  
Author(s):  
Amrita Dawn ◽  
Shailja Singh ◽  
Kunal R. More ◽  
Faiza Amber Siddiqui ◽  
Niseema Pachikara ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Human Erythrocytes ◽  
Merozoite Invasion ◽  
Falciparum Merozoite
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