Plasmodium CDP-DAG synthase: an atypical gene with an essential N-terminal extension.

Autor: Shastri S; CNRS UMR5235, University of Montpellier 2, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France., Zeeman AM, Berry L, Verburgh RJ, Braun-Breton C, Thomas AW, Gannoun-Zaki L, Kocken CH, Vial HJ
Jazyk: angličtina
Zdroj: International journal for parasitology [Int J Parasitol] 2010 Sep; Vol. 40 (11), pp. 1257-68. Date of Electronic Publication: 2010 Apr 10.
DOI: 10.1016/j.ijpara.2010.03.006
Abstrakt: Cytidine diphosphate diacylglycerol synthase (CDS) diverts phosphatidic acid towards the biosynthesis of CDP-DAG, an obligatory liponucleotide intermediate in anionic phospholipid biosynthesis. The 78kDa predicted Plasmodium falciparum CDS (PfCDS) is recovered as a 50 kDa conserved C-terminal cytidylyltransferase domain (C-PfCDS) and a 28kDa fragment that corresponds to the unusually long hydrophilic asparagine-rich N-terminal extension (N-PfCDS). Here, we show that the two fragments of PfCDS are the processed forms of the 78 kDa pro-form that is encoded from a single transcript with no alternate translation start site for C-PfCDS. PfCDS, which shares 54% sequence identity with Plasmodium knowlesi CDS (PkCDS), could substitute for PkCDS in P. knowlesi. Experiments to disrupt either the full-length or the N-terminal extension of PkCDS indicate that not only the C-terminal cytidylyltransferase domain but also the N-terminal extension is essential to Plasmodium spp. PkCDS and PfCDS introduced in P. knowlesi were processed in the parasite, suggesting a conserved parasite-dependent mechanism. The N-PfCDS appears to be a peripheral membrane protein and is trafficked outside the parasite to the parasitophorous vacuole. Although the function of this unusual N-PfCDS remains enigmatic, the study here highlights features of this essential gene and its biological importance during the intra-erythrocytic cycle of the parasite.
(Copyright (c) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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