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Lipid remodelling of glycosylphosphatidylinositol (GPI) glycoconjugates in procyclic-form trypanosomes: biosynthesis and processing of GPIs revisited

Bütikofer, Peter, Greganova, Eva, Liu, Yuk‑Chien, Edwards, Ian J., Lehane, Mike and Acosta Serrano, Alvaro ORCID: https://orcid.org/0000-0002-2576-7959 (2010) 'Lipid remodelling of glycosylphosphatidylinositol (GPI) glycoconjugates in procyclic-form trypanosomes: biosynthesis and processing of GPIs revisited'. Biochemical Journal, Vol 428, Issue 3, pp. 409-418.

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Abstract

The African trypanosome, Trypanosoma brucei, has been used as a model to study the biosynthesis of GPI (glycosylphosphatidylinositol)anchors. In mammalian (bloodstream)-form parasites, diacyl-type GPI precursors are remodelled in their lipid moieties before attachment to variant surface glycoproteins. In contrast,the GPI precursors of insect (procyclic)-form parasites, consisting
of lyso-(acyl)PI (inositol-acylated acyl-lyso-phosphatidylinositol)species, remain unaltered before protein attachment. By using a combination of metabolic labelling, cell-free assays and complementary MS analyses, we show in the present study that GPIanchored glycoconjugates in T. congolense procyclic forms initially
receive tri-acylated GPI precursors, which are subsequently
de-acylated either at the glycerol backbone or on the inositol ring. Chemical and enzymatic treatments of [3H]myristate-labelled lipids in combination with ESI-MS/MS (electrospray ionizationtandem MS) and MALDI-QIT-TOF-MS3 (matrix-assisted laserdesorption ionization–quadrupole ion trap–time-of-flight MS)analyses indicate that the structure of the lipid moieties of steadystate GPI lipids from T. congolense procyclic forms consist of a mixture of lyso-(acyl)PI, diacyl-PI and diacyl-(acyl)PI species. Interestingly, some of these species are myristoylated at the sn-2 position. To our knowledge, this is the first demonstration of lipid remodelling at the level of protein- or polysaccharide-linked GPIanchors in procyclic-form trypanosomes.

Item Type: Article
Uncontrolled Keywords: glycosylphosphatidylinositol (GPI), lipid biosynthesis, lipid remodelling, mass spectrometry (MS), posttranslational modification, trypanosome.
Subjects: QX Parasitology > Protozoa > QX 70 Mastigophora. (e.g., Giardia. Trichomonas. Trypanosoma. Leishmania)
QU Biochemistry > QU 4 General works
Faculty: Department: Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI): https://doi.org/10.1042/BJ20100229
Depositing User: Users 183 not found.
Date Deposited: 07 Jul 2010 14:42
Last Modified: 27 Sep 2019 15:29
URI: https://archive.lstmed.ac.uk/id/eprint/1009

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