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The arginine sensing and transport binding sites are distinct in the human pathogen Leishmania.
- Source :
-
PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2019 Apr 24; Vol. 13 (4), pp. e0007304. Date of Electronic Publication: 2019 Apr 24 (Print Publication: 2019). - Publication Year :
- 2019
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Amino Acid Transport Systems, Basic genetics
Arginine analogs & derivatives
Binding Sites
Biological Transport
Gene Expression Regulation
Humans
Leishmania donovani genetics
Macrophages parasitology
Phagosomes parasitology
Protozoan Proteins genetics
THP-1 Cells
Amino Acid Transport Systems, Basic metabolism
Arginine metabolism
Leishmania donovani metabolism
Protozoan Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1935-2735
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PLoS neglected tropical diseases
- Publication Type :
- Academic Journal
- Accession number :
- 31017889
- Full Text :
- https://doi.org/10.1371/journal.pntd.0007304