Plasmodium CDP-DAG synthase: an atypical gene with an essential N-terminal extension.
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.
Shastri
Shilpa
S
CNRS UMR5235, University of Montpellier 2, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France.
Zeeman
Anne-Marie
AM
Berry
Laurence
L
Verburgh
R Joyce
RJ
Braun-Breton
Catherine
C
Thomas
Alan W
AW
Gannoun-Zaki
Laila
L
Kocken
Clemens H M
CH
Vial
Henri J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D003567:Cytidine Diphosphate Diglycerides / Q000096:biosynthesis; D002798:Diacylglycerol Cholinephosphotransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000469:parasitology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D016790:Plasmodium knowlesi / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D003567:Cytidine Diphosphate Diglycerides; D015800:Protozoan Proteins; D002798:Diacylglycerol Cholinephosphotransferase