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- Title
The arginine sensing and transport binding sites are distinct in the human pathogen Leishmania.
- Authors
Pawar, Harsh; Puri, Madhu; Fischer Weinberger, Renana; Madhubala, Rentala; Zilberstein, Dan
- 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.
- Subjects
LEISHMANIA mexicana; BINDING sites; VISCERAL leishmaniasis; LEISHMANIA; LEISHMANIA donovani; ARGININE
- Publication
PLoS Neglected Tropical Diseases, 2019, Vol 13, Issue 4, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0007304