Journal
EXPERIMENTAL PARASITOLOGY
Volume 116, Issue 2, Pages 182-189Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.exppara.2006.12.008
Keywords
Leishmania donovani; clinical isolate; pteridine reductase 1; protein degradation; proteasome; metacyclogenesis; pteridine reductase 1; green fluorescent protein; multivesicular tubule lysosome; phosphate-buffered saline; (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid); heat-inactivated fetal bovine serum; electrochemiluminescence; fluorescence activated cell sorting; dithiothreitol; sodium dodecyl sulfate; polyacrylamide gel electrophoresis
Categories
Ask authors/readers for more resources
Pteridine reductase 1 (PTR1) is an essential enzyme of pterin and folate metabolism in the protozoan parasite Leishmania. The present work is focused on the degradation of PTR1 during growth phase in Leishmania donovani. Western blot analysis with PTR1-GFP transfected promastigotes revealed that PTR1 protein was degraded in the stationary phase of growth at the time when the parasites were undergoing metacyclogenesis. Fluorescence microscopy revealed cytoplasmic localization of GFP tagged protein extending to the flagellum in these stationary phase promastigotes, implying that degradation of the protein was not by the usual multivesicular tubule lysosome (MVT) pathway. A probable destruction box of nine amino acids Q63ADLSNVAK71 and possible lysine residue K156 was identified in L. donovani PTR1 to be the site for ubiquitin conjugation. This suggests that PTR1 degradation during the stationary phase of growth is mediated by the proteasome. This leads to lower levels of H4-biopterin, which favors metacyclogenesis, and subsequently results in a highly infective stage of the parasite. Therefore, this finding has importance to identify new target molecule like the proteasome for therapeutic intervention. (c) 2007 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available