Functional Analysis of the First Mannosyltransferase (PIG-M) involved in Glycosylphosphatidylinositol Synthesis in Plasmodium falciparum

  • Kim, Youn Uck (Department of Biological Sciences, Sun Moon University) ;
  • Hong, Yeongjin (Genomic Research Center for Enteropathogenic Bacteria and Department of Microbiology, Chonnam National University Medical School)
  • Received : 2007.01.04
  • Accepted : 2007.05.31
  • Published : 2007.10.31

Abstract

The mammalian glycosylphosphatidylinositol (GPI) anchor consists of three mannoses attached to acylated GlcN-(acyl)PI to form $Man_3$-GlcN-(acyl)PI. The first of the three mannose groups is attached to an intermediate to generate Man-GlcN-(acyl)PI by the first mannosyltransferase (GPI-MT-I). Mammalian and protozoan GPI-MT-I have different substrate specificities. PIG-M encodes the mammalial GPI-MT-I which has 423 amino acids and multiple transmembrane domains. In this work we cloned PIG-M homologues from humans, Plasmodium falciparum (PfPIG-M), and Saccharomyces cerevisiae (GPI14), to test whether they could complement GPI-MT-I-deficient mammalian cells, since this biosynthetic step is likely to be a good target for selective screening of inhibitors against many pathogenic organisms. PfPIG-M partially restored cell surface expression of the GPI-anchored protein CD59 in PIG-M deficient mammalian cells, and first mannose transfer activity in vitro; however, this was not the case for GPI14.

Keywords

GPI;GPI-MT-I;PIG-M;Plasmodium falciparum;Saccharomyces cerevisiae

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF), Ministry of Commerce, Industry, and Energy (MOCIE)

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