Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells.

Manuel Castro de Moura, Francesc Miro, Jung Min Han, Sunghoon Kim, Antonio Celada, Lluís Ribas de Pouplana

Research output: Contribution to journalArticle

Abstract

Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

Original languageEnglish
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number11
Publication statusPublished - 2011 Nov 1

Fingerprint

Lysine-tRNA Ligase
Entamoeba
Chemokines
Human Activities
Endothelial Cells
Cytokines
Amino Acyl-tRNA Synthetases
Peptides
Parasites
Transfer RNA Aminoacylation
Entamoeba histolytica
Chemotactic Factors
Protein Sorting Signals
Site-Directed Mutagenesis
Peptide Hydrolases
Pressure
Enzymes

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Castro de Moura, Manuel ; Miro, Francesc ; Han, Jung Min ; Kim, Sunghoon ; Celada, Antonio ; Ribas de Pouplana, Lluís. / Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 11.
@article{03d25d14af4d436c8a914f0e1fc593ee,
title = "Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells.",
abstract = "Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.",
author = "{Castro de Moura}, Manuel and Francesc Miro and Han, {Jung Min} and Sunghoon Kim and Antonio Celada and {Ribas de Pouplana}, Llu{\'i}s",
year = "2011",
month = "11",
day = "1",
language = "English",
volume = "5",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",
number = "11",

}

Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells. / Castro de Moura, Manuel; Miro, Francesc; Han, Jung Min; Kim, Sunghoon; Celada, Antonio; Ribas de Pouplana, Lluís.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 11, 01.11.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells.

AU - Castro de Moura, Manuel

AU - Miro, Francesc

AU - Han, Jung Min

AU - Kim, Sunghoon

AU - Celada, Antonio

AU - Ribas de Pouplana, Lluís

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

AB - Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

UR - http://www.scopus.com/inward/record.url?scp=84859189464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859189464&partnerID=8YFLogxK

M3 - Article

C2 - 22140588

VL - 5

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

IS - 11

ER -