Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands

ABSTRACT Invasion of erythrocytes by Plasmodium falciparum requires a connection between the cytoplasmic tail of the parasite’s ligands for its erythrocyte receptors and the actin-myosin motor of the parasite. For the thromobospondin-related anonymous protein (TRAP) ligand on Plasmodium sporozoites,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ipsita Pal-Bhowmick, John Andersen, Prakash Srinivasan, David L. Narum, Jürgen Bosch, Louis H. Miller
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a8130b2b91af4fe3aae3ea5c960eb93d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a8130b2b91af4fe3aae3ea5c960eb93d
record_format	dspace
spelling	oai:doaj.org-article:a8130b2b91af4fe3aae3ea5c960eb93d2021-11-15T15:39:12ZBinding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands10.1128/mBio.00292-122150-7511https://doaj.org/article/a8130b2b91af4fe3aae3ea5c960eb93d2012-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00292-12https://doaj.org/toc/2150-7511ABSTRACT Invasion of erythrocytes by Plasmodium falciparum requires a connection between the cytoplasmic tail of the parasite’s ligands for its erythrocyte receptors and the actin-myosin motor of the parasite. For the thromobospondin-related anonymous protein (TRAP) ligand on Plasmodium sporozoites, aldolase forms this connection and requires tryptophan and negatively charged amino acids in the ligand’s cytoplasmic tail. Because of the importance of the Duffy binding-like (DBL) and the reticulocyte homology (RH) ligand families in erythrocyte binding and merozoite invasion, we characterized the ability of their cytoplasmic tails to bind aldolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), both of which bind actin. We tested the binding of the cytoplasmic peptides of the two ligand families to aldolase and GAPDH. Only the cytoplasmic peptides of some RH ligands showed strong binding to aldolase, and the binding depended on the presence of an aromatic amino acid (phenylalanine or tyrosine), rather than tryptophan, in the context of negatively charged amino acids. The binding was confirmed by surface plasmon resonance analysis and was found to represent affinity similar to that seen with TRAP. An X-ray crystal structure of aldolase at 2.5 Å in the presence of RH2b peptide suggested that the binding site location was near the TRAP-binding site. GAPDH bound to some of the cytoplasmic tails of certain RH and DBL ligands in an aromatic amino acid-dependent manner. Thus, the connection between Plasmodium merozoite ligands and erythrocyte receptors and the actin motor can be achieved through the activity of either aldolase or GAPDH by mechanisms that do not require tryptophan but, rather, other aromatic amino acids. IMPORTANCE The invasion of the Plasmodium merozoite into erythrocytes is a critical element in malaria pathogenesis. It is important to understand the molecular details of this process, as this machinery can be a target for both vaccine and drug development. In Plasmodium sporozoites and Toxoplasma tachyzoites, invasion involves a glycolytic enzyme aldolase, linking the cytoplasmic tail domains of the parasite ligands to the actin-myosin motor that drives invasion. This binding requires a tryptophan that cannot be replaced by other aromatic residues. Here we show that aldolase binds the cytoplasmic tails of some P. falciparum merozoite erythrocyte-binding ligands but that the binding involves aromatic residues other than tryptophan. The biological relevance of aldolase binding to cytoplasmic tails of parasite ligands in invasion is demonstrated by our observation that RH2b but not RH2a binds to aldolase and, as previously shown, that RH2b but not RH2a is required for P. falciparum invasion of erythrocytes.Ipsita Pal-BhowmickJohn AndersenPrakash SrinivasanDavid L. NarumJürgen BoschLouis H. MillerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 5 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Ipsita Pal-Bhowmick John Andersen Prakash Srinivasan David L. Narum Jürgen Bosch Louis H. Miller Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
description	ABSTRACT Invasion of erythrocytes by Plasmodium falciparum requires a connection between the cytoplasmic tail of the parasite’s ligands for its erythrocyte receptors and the actin-myosin motor of the parasite. For the thromobospondin-related anonymous protein (TRAP) ligand on Plasmodium sporozoites, aldolase forms this connection and requires tryptophan and negatively charged amino acids in the ligand’s cytoplasmic tail. Because of the importance of the Duffy binding-like (DBL) and the reticulocyte homology (RH) ligand families in erythrocyte binding and merozoite invasion, we characterized the ability of their cytoplasmic tails to bind aldolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), both of which bind actin. We tested the binding of the cytoplasmic peptides of the two ligand families to aldolase and GAPDH. Only the cytoplasmic peptides of some RH ligands showed strong binding to aldolase, and the binding depended on the presence of an aromatic amino acid (phenylalanine or tyrosine), rather than tryptophan, in the context of negatively charged amino acids. The binding was confirmed by surface plasmon resonance analysis and was found to represent affinity similar to that seen with TRAP. An X-ray crystal structure of aldolase at 2.5 Å in the presence of RH2b peptide suggested that the binding site location was near the TRAP-binding site. GAPDH bound to some of the cytoplasmic tails of certain RH and DBL ligands in an aromatic amino acid-dependent manner. Thus, the connection between Plasmodium merozoite ligands and erythrocyte receptors and the actin motor can be achieved through the activity of either aldolase or GAPDH by mechanisms that do not require tryptophan but, rather, other aromatic amino acids. IMPORTANCE The invasion of the Plasmodium merozoite into erythrocytes is a critical element in malaria pathogenesis. It is important to understand the molecular details of this process, as this machinery can be a target for both vaccine and drug development. In Plasmodium sporozoites and Toxoplasma tachyzoites, invasion involves a glycolytic enzyme aldolase, linking the cytoplasmic tail domains of the parasite ligands to the actin-myosin motor that drives invasion. This binding requires a tryptophan that cannot be replaced by other aromatic residues. Here we show that aldolase binds the cytoplasmic tails of some P. falciparum merozoite erythrocyte-binding ligands but that the binding involves aromatic residues other than tryptophan. The biological relevance of aldolase binding to cytoplasmic tails of parasite ligands in invasion is demonstrated by our observation that RH2b but not RH2a binds to aldolase and, as previously shown, that RH2b but not RH2a is required for P. falciparum invasion of erythrocytes.
format	article
author	Ipsita Pal-Bhowmick John Andersen Prakash Srinivasan David L. Narum Jürgen Bosch Louis H. Miller
author_facet	Ipsita Pal-Bhowmick John Andersen Prakash Srinivasan David L. Narum Jürgen Bosch Louis H. Miller
author_sort	Ipsita Pal-Bhowmick
title	Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
title_short	Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
title_full	Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
title_fullStr	Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
title_full_unstemmed	Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands
title_sort	binding of aldolase and glyceraldehyde-3-phosphate dehydrogenase to the cytoplasmic tails of <named-content content-type="genus-species">plasmodium falciparum</named-content> merozoite duffy binding-like and reticulocyte homology ligands
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/a8130b2b91af4fe3aae3ea5c960eb93d
work_keys_str_mv	AT ipsitapalbhowmick bindingofaldolaseandglyceraldehyde3phosphatedehydrogenasetothecytoplasmictailsofnamedcontentcontenttypegenusspeciesplasmodiumfalciparumnamedcontentmerozoiteduffybindinglikeandreticulocytehomologyligands AT johnandersen bindingofaldolaseandglyceraldehyde3phosphatedehydrogenasetothecytoplasmictailsofnamedcontentcontenttypegenusspeciesplasmodiumfalciparumnamedcontentmerozoiteduffybindinglikeandreticulocytehomologyligands AT prakashsrinivasan bindingofaldolaseandglyceraldehyde3phosphatedehydrogenasetothecytoplasmictailsofnamedcontentcontenttypegenusspeciesplasmodiumfalciparumnamedcontentmerozoiteduffybindinglikeandreticulocytehomologyligands AT davidlnarum bindingofaldolaseandglyceraldehyde3phosphatedehydrogenasetothecytoplasmictailsofnamedcontentcontenttypegenusspeciesplasmodiumfalciparumnamedcontentmerozoiteduffybindinglikeandreticulocytehomologyligands AT jurgenbosch bindingofaldolaseandglyceraldehyde3phosphatedehydrogenasetothecytoplasmictailsofnamedcontentcontenttypegenusspeciesplasmodiumfalciparumnamedcontentmerozoiteduffybindinglikeandreticulocytehomologyligands AT louishmiller bindingofaldolaseandglyceraldehyde3phosphatedehydrogenasetothecytoplasmictailsofnamedcontentcontenttypegenusspeciesplasmodiumfalciparumnamedcontentmerozoiteduffybindinglikeandreticulocytehomologyligands
_version_	1718427786221191168

Binding of Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase to the Cytoplasmic Tails of <named-content content-type="genus-species">Plasmodium falciparum</named-content> Merozoite Duffy Binding-Like and Reticulocyte Homology Ligands

Ejemplares similares