Home
Group
Research
Teaching
Links
Institute
 

Attachment of Proteins to Membranes via Lipids

Trypanosoma brucei was a key player in the discovery of glycosylphosphatidylinositol (GPI) anchors: the first complete chemical structure of a GPI anchor was determined using the variant surface glycoprotein, the major surface protein of T. brucei bloodstream forms, as a model protein. In addition, the biosynthetic steps leading to the assembly of GPI anchors were first identified in T. brucei and provided the groundwork to establish these pathways in other cells.

GPI-anchored molecules in procyclic form trypanosomes
We have been interested to identify novel GPI-anchored molecules in trypanosomes and to study their (additional) posttranslational modifications and roles during the parasite life cycle. Our work lead to the discovery of GPEET procyclin, a major surface protein of T. brucei procyclic forms during the early stage of an infection in the tsetse fly midgut. Interestingly, we found that GPEET is phosphorylated, which is an unusual modification for a surface protein. The membrane-associated kinase responsible for GPEET phosphorylation was found to be co-expressed with its substrate during the parasite life cycle.

Scheme for GPEET trafficking and phosphorylation by GPEET kinase in T. brucei procyclic forms (see Bütikofer et al., J. Cell. Sci 112, 1785-1795, 1999; Schlaeppi et al., J. Biol. Chem. 278, 49980-49987, 2003).

In addition, we discovered two novel GPI-anchored molecules in T. congolense procyclic forms, PRS and EPGENGT procyclin. While PRS may be a non-proteinacious surface molecule, EPGENGT procyclin represents the first repetitive surface protein in T. congolense thereby resembling the EP and GPEET procyclins from T. brucei. Our studies show that PRS is a surface marker for trypanosomes early during fly infection while EPGENGT procyclin is continuously expressed on parasites in the fly midgut.

Structure of EPGENGT procyclin, a major GPI-anchored surface glycoprotein of T. congolense procyclic forms (Utz et al., Eukaryot. Cell 5, 1430-1440, 2006).

EPG modification of eEF1A

We have also been interested in a rare and unusual protein modification that has been discovered in elongation factor 1A (eEF1A) and involves the covalent attachment of ethanolamine-phosphoglycerol (EPG) to two glutamic acids residues. Using T. brucei as a model organism, we studied the biosynthetic steps leading to this modification to investigate its possible biological function. Our results showed that the phospholipid phosphatidylethanolamine is the precursor of the EPG moiety of T. brucei eEF1A.

Structure of EPG attached to glu362 in T. brucei eEF1A (Signorell et al., J. Biol. Chem. 283, 20320-20329, 2008).

<< back

Home
Group
Research
Teaching
Links
Institute