The arginine sensing and transport binding sites are distinct in the human pathogen Leishmania.
PLoS Negl Trop Dis
; 13(4): e0007304, 2019 04.
Article
de En
| MEDLINE
| ID: mdl-31017889
ABSTRACT
The intracellular protozoan parasite Leishmania donovani causes human visceral leishmaniasis. Intracellular L. donovani that proliferate inside macrophage phagolysosomes compete with the host for arginine, creating a situation that endangers parasite survival. Parasites have a sensor that upon arginine deficiency activates an Arginine Deprivation Response (ADR). L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by ADR in intracellular amastigotes. To date, the sensor and its ligand have not been identified. Here, we show that the conserved amidino group at the distal cap of the arginine side chain is the ligand that activates ADR, in both promastigotes and intracellular amastigotes, and that arginine sensing and transport binding sites are distinct in L. donovani. Finally, upon addition of arginine and analogues to deprived cells, the amidino ligand activates rapid degradation of LdAAP3. This study provides the first identification of an intra-molecular ligand of a sensor that acts during infection.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Arginine
/
Leishmania donovani
/
Protéines de protozoaire
/
Systèmes de transport d'acides aminés basiques
Limites:
Humans
Langue:
En
Journal:
PLoS Negl Trop Dis
Sujet du journal:
MEDICINA TROPICAL
Année:
2019
Type de document:
Article
Pays d'affiliation:
Israël