title: Plasmodium berghei glycine cleavage system T-protein is non-essential for parasite survival in vertebrate and invertebrate hosts.
abstract: T-protein, an aminomethyltransferase, represents one of the four components of glycine cleavage system (GCS) and catalyzes the transfer of methylene group from H-protein intermediate to tetrahydrofolate (THF) forming N(5), N(10)-methylene THF (CH2-THF) with the release of ammonia. The malaria parasite genome encodes T-, H- and L-proteins, but not P-protein which is a glycine decarboxylase generating the aminomethylene group. A putative GCS has been considered to be functional in the parasite mitochondrion despite the absence of a detectable P-protein homologue. In the present study, the mitochondrial localization of T-protein in the malaria parasite was confirmed by immunofluorescence and its essentiality in the entire parasite life cycle was studied by targeting the T-protein locus in Plasmodium berghei (Pb). PbT knock out parasites did not show any growth defect in asexual, sexual and liver stages indicating that the T-protein is dispensable for parasite survival in vertebrate and invertebrate hosts. The absence of P-protein homologue and the non-essentiality of T protein suggest the possible redundancy of GCS activity in the malaria parasite. Nevertheless, the H- and L-proteins of GCS could be essential for malaria parasite because of their involvement in α-ketoacid dehydrogenase reactions.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Nandan Mysore
authors.initials: NM
authors.lastname: Varadarajan
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Balamurugan
authors.initials: B
authors.lastname: Sundaram
authors.affiliation: National Institute of Malaria Research (Field Unit), Nirmal Bhawan, ICMR Complex, Poojanahalli, Off NH-7, Kannamangala Post, Bangalore 562 110, India.
authors.forename: Pradeep Annamalai
authors.initials: PA
authors.lastname: Subramani
authors.affiliation: National Institute of Malaria Research (Field Unit), Nirmal Bhawan, ICMR Complex, Poojanahalli, Off NH-7, Kannamangala Post, Bangalore 562 110, India.
authors.forename: Devaiah Monnanda
authors.initials: DM
authors.lastname: Kalappa
authors.affiliation: National Institute of Malaria Research (Field Unit), Nirmal Bhawan, ICMR Complex, Poojanahalli, Off NH-7, Kannamangala Post, Bangalore 562 110, India.
authors.forename: Susanta Kumar
authors.initials: SK
authors.lastname: Ghosh
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India; Centre for Infectious Disease Research, Indian Institute of Science, Bangalore 560 012, India. Electronic address: arunv@biochem.iisc.ernet.in.
authors.forename: Viswanathan Arun
authors.initials: VA
authors.lastname: Nagaraj
mesh_terms: D050960:Aminomethyltransferase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D020043:Genes, Essential; D008018:Life Cycle Stages; D051379:Mice; D010641:Phenotype; D010962:Plasmodium berghei / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D050960:Aminomethyltransferase
keywords: Glycine cleavage system; Knock out; Mitochondrion; Plasmodium berghei; Plasmodium falciparum; T-protein