Analysis of glycosylphosphatidylinositol protein anchors: the prion protein.

Membrane proteins constitute a substantial fraction of the human proteome. A small subgroup associates with membranes through the presence of a C-terminal lipid anchor that is joined to the protein via a phosphoglycan. The prion protein (PrP), an abnormally folded form that causes fatal neurodegeneration, is one example of a glycosylphosphatidylinositol (GPI)-anchored protein. Although GPI-anchored proteins were first recognized some 20 years ago (in the mid-1980s), relatively few GPI anchors have been analyzed in detail. Therefore, a description of the analysis of the PrP-GPI anchor using a variety of mass spectrometric methods is of interest even though some of the approaches adopted could be facilitated through the use of newer, more sensitive techniques.