Characterization of Plasmodium falciparum integral membrane protein Pf25-IMP and identification of its red blood cell binding sequences inhibiting merozoite invasion in vitro

Hernando Curtidor, Gabriela Arévalo, Magnolia Vanegas, Carolina Vizcaíno, Manuel A. Patarroyo, Martha Forero, Manuel E. Patarroyo

Resultado de la investigación: Contribución a RevistaArtículo

14 Citas (Scopus)

Resumen

The identification of proteins present on the surface of Plasmodium falciparum-infected red blood cells as well as of free merozoites has been widely considered as one of the main areas of research in the development of an antimalarial vaccine due to their involvement in the parasite's pathogenesis and invasion mechanisms. Major advances had been accomplished in this area thanks to the analysis of the reported genomic sequence of P. falciparum, allowing for the identification of genes encoding for putative integral membrane proteins. This study reports for the first time the transcription of the MAL8P1.3 gene, which codifies for a 25-kDa integral membrane protein of P. falciparum (FCB-2 strain), namely, Pf25-IMP. Western blot and immunofluorescence assays using goat polyclonal sera indicate that this protein is expressed in erythrocytic asexual blood stages. A highly robust, sensible, and specific receptor-ligand interaction assay allowed identification of two high activity binding peptides (HABPs) derived from Pf25-IMP: 30577 (41YKTANENVKLASSLSDRLSR 60) and 30583 (161LNKKTVVRKIAEGLGYTIVF180). Both HABPs bound with high affinity to human red blood cells (RBCs), and such binding was susceptible to enzyme treatment with trypsin. A common RBC surface receptor of apparently 48 kDa was found for both HABPs, plus an additional 31-kDa receptor for HABP 30577. HABP 30577 inhibited merozoite invasion in vitro by 73%, while HABP 30583 showed a 59% inhibition at 200 μM concentration. The data suggest a possible role of Pf25-IMP in merozoite invasion to RBCs and support its inclusion in further immunological studies for evaluating its potential as vaccine candidates. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 The Protein Society.
Idioma originalEnglish (US)
Páginas (desde-hasta)1494-1504
Número de páginas11
PublicaciónProtein Science
DOI
EstadoPublished - sep 1 2008

Huella dactilar

Merozoites
Inosine Monophosphate
Plasmodium falciparum
Membrane Proteins
Blood
Erythrocytes
Cells
Peptides
Assays
Vaccines
Gene encoding
Antimalarials
Cell Surface Receptors
Transcription
Ports and harbors
Goats
Trypsin
Genes
Fluorescent Antibody Technique
In Vitro Techniques

Citar esto

Curtidor, Hernando ; Arévalo, Gabriela ; Vanegas, Magnolia ; Vizcaíno, Carolina ; Patarroyo, Manuel A. ; Forero, Martha ; Patarroyo, Manuel E. / Characterization of Plasmodium falciparum integral membrane protein Pf25-IMP and identification of its red blood cell binding sequences inhibiting merozoite invasion in vitro. En: Protein Science. 2008 ; pp. 1494-1504.
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title = "Characterization of Plasmodium falciparum integral membrane protein Pf25-IMP and identification of its red blood cell binding sequences inhibiting merozoite invasion in vitro",
abstract = "The identification of proteins present on the surface of Plasmodium falciparum-infected red blood cells as well as of free merozoites has been widely considered as one of the main areas of research in the development of an antimalarial vaccine due to their involvement in the parasite's pathogenesis and invasion mechanisms. Major advances had been accomplished in this area thanks to the analysis of the reported genomic sequence of P. falciparum, allowing for the identification of genes encoding for putative integral membrane proteins. This study reports for the first time the transcription of the MAL8P1.3 gene, which codifies for a 25-kDa integral membrane protein of P. falciparum (FCB-2 strain), namely, Pf25-IMP. Western blot and immunofluorescence assays using goat polyclonal sera indicate that this protein is expressed in erythrocytic asexual blood stages. A highly robust, sensible, and specific receptor-ligand interaction assay allowed identification of two high activity binding peptides (HABPs) derived from Pf25-IMP: 30577 (41YKTANENVKLASSLSDRLSR 60) and 30583 (161LNKKTVVRKIAEGLGYTIVF180). Both HABPs bound with high affinity to human red blood cells (RBCs), and such binding was susceptible to enzyme treatment with trypsin. A common RBC surface receptor of apparently 48 kDa was found for both HABPs, plus an additional 31-kDa receptor for HABP 30577. HABP 30577 inhibited merozoite invasion in vitro by 73{\%}, while HABP 30583 showed a 59{\%} inhibition at 200 μM concentration. The data suggest a possible role of Pf25-IMP in merozoite invasion to RBCs and support its inclusion in further immunological studies for evaluating its potential as vaccine candidates. Published by Cold Spring Harbor Laboratory Press. Copyright {\circledC} 2008 The Protein Society.",
author = "Hernando Curtidor and Gabriela Ar{\'e}valo and Magnolia Vanegas and Carolina Vizca{\'i}no and Patarroyo, {Manuel A.} and Martha Forero and Patarroyo, {Manuel E.}",
year = "2008",
month = "9",
day = "1",
doi = "10.1110/ps.036251.108",
language = "English (US)",
pages = "1494--1504",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Cold Spring Harbor Laboratory Press",

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Characterization of Plasmodium falciparum integral membrane protein Pf25-IMP and identification of its red blood cell binding sequences inhibiting merozoite invasion in vitro. / Curtidor, Hernando; Arévalo, Gabriela; Vanegas, Magnolia; Vizcaíno, Carolina; Patarroyo, Manuel A.; Forero, Martha; Patarroyo, Manuel E.

En: Protein Science, 01.09.2008, p. 1494-1504.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Characterization of Plasmodium falciparum integral membrane protein Pf25-IMP and identification of its red blood cell binding sequences inhibiting merozoite invasion in vitro

AU - Curtidor, Hernando

AU - Arévalo, Gabriela

AU - Vanegas, Magnolia

AU - Vizcaíno, Carolina

AU - Patarroyo, Manuel A.

AU - Forero, Martha

AU - Patarroyo, Manuel E.

PY - 2008/9/1

Y1 - 2008/9/1

N2 - The identification of proteins present on the surface of Plasmodium falciparum-infected red blood cells as well as of free merozoites has been widely considered as one of the main areas of research in the development of an antimalarial vaccine due to their involvement in the parasite's pathogenesis and invasion mechanisms. Major advances had been accomplished in this area thanks to the analysis of the reported genomic sequence of P. falciparum, allowing for the identification of genes encoding for putative integral membrane proteins. This study reports for the first time the transcription of the MAL8P1.3 gene, which codifies for a 25-kDa integral membrane protein of P. falciparum (FCB-2 strain), namely, Pf25-IMP. Western blot and immunofluorescence assays using goat polyclonal sera indicate that this protein is expressed in erythrocytic asexual blood stages. A highly robust, sensible, and specific receptor-ligand interaction assay allowed identification of two high activity binding peptides (HABPs) derived from Pf25-IMP: 30577 (41YKTANENVKLASSLSDRLSR 60) and 30583 (161LNKKTVVRKIAEGLGYTIVF180). Both HABPs bound with high affinity to human red blood cells (RBCs), and such binding was susceptible to enzyme treatment with trypsin. A common RBC surface receptor of apparently 48 kDa was found for both HABPs, plus an additional 31-kDa receptor for HABP 30577. HABP 30577 inhibited merozoite invasion in vitro by 73%, while HABP 30583 showed a 59% inhibition at 200 μM concentration. The data suggest a possible role of Pf25-IMP in merozoite invasion to RBCs and support its inclusion in further immunological studies for evaluating its potential as vaccine candidates. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 The Protein Society.

AB - The identification of proteins present on the surface of Plasmodium falciparum-infected red blood cells as well as of free merozoites has been widely considered as one of the main areas of research in the development of an antimalarial vaccine due to their involvement in the parasite's pathogenesis and invasion mechanisms. Major advances had been accomplished in this area thanks to the analysis of the reported genomic sequence of P. falciparum, allowing for the identification of genes encoding for putative integral membrane proteins. This study reports for the first time the transcription of the MAL8P1.3 gene, which codifies for a 25-kDa integral membrane protein of P. falciparum (FCB-2 strain), namely, Pf25-IMP. Western blot and immunofluorescence assays using goat polyclonal sera indicate that this protein is expressed in erythrocytic asexual blood stages. A highly robust, sensible, and specific receptor-ligand interaction assay allowed identification of two high activity binding peptides (HABPs) derived from Pf25-IMP: 30577 (41YKTANENVKLASSLSDRLSR 60) and 30583 (161LNKKTVVRKIAEGLGYTIVF180). Both HABPs bound with high affinity to human red blood cells (RBCs), and such binding was susceptible to enzyme treatment with trypsin. A common RBC surface receptor of apparently 48 kDa was found for both HABPs, plus an additional 31-kDa receptor for HABP 30577. HABP 30577 inhibited merozoite invasion in vitro by 73%, while HABP 30583 showed a 59% inhibition at 200 μM concentration. The data suggest a possible role of Pf25-IMP in merozoite invasion to RBCs and support its inclusion in further immunological studies for evaluating its potential as vaccine candidates. Published by Cold Spring Harbor Laboratory Press. Copyright © 2008 The Protein Society.

U2 - 10.1110/ps.036251.108

DO - 10.1110/ps.036251.108

M3 - Article

SP - 1494

EP - 1504

JO - Protein Science

JF - Protein Science

SN - 0961-8368

ER -