Chemistry Reference
In-Depth Information
9
Glycosylphosphatidylinositol Anchors: Structure,
Biosynthesis and Functions
Hosam Shams - Eldin , Fran ç oise Debierre - Grockiego , and Ralph T. Schwarz
Previous chapters (and also Chapter 11) have illustrated several key points about
how protein backbones can be glycosylated, defi ning both
N
- and
O
- glycosylation
as common features in evolution. As will be seen, especially in Chapters 10 and
30, lipids establish the second class of backbone for glycan conjugations. This
chapter deals with a hybrid form, in which a glycan structure forms a bridge
between a protein and a lipid anchor, which attaches the protein to a membrane.
Evidently, this structure substitutes for a membrane-integrating part of the protein.
These structures are called glycosylphosphatidylinositol ( GPI ) membrane anchors.
This chapter fi rst defi nes their structure, then presents methods used for their
detection or isolation, outlines their biosynthesis and defects in their biosynthesis,
and fi nally presents a survey of general as well as specialized functions.
9.1
Structure of GPI Anchors
The basic structure of a GPI anchor is given in Figure 9.1 (for abbreviations of
sugar names, please see Figure 1.6). It consists of ethanolamine, mannose,
nonacetylated glucosamine, inositol (the most prominent, naturally occurring
form is
myo
- inositol,
cis
- 1,2,3,5 -
trans
- 4,6 - cyclohexanehexol) and a lipid moiety;
in part linked by diphosphate bridges. It is commonly abbreviated as
ethanolamine6Man
1 - 4GlcN1 - 6inositolphosphate lipid (Figure
9.1, upper part). This structure thus connects a protein with the lipid - the integral
membrane part. GPIs are widespread among eukaryotes, and the expression of
GPI-anchored proteins and free GPIs is particularly abundant among the parasitic
protozoa. To date, several hundred GPI membrane proteins are known from pro-
tozoa, yeasts, fungi, plants and mammals (Table 9.1). Initially, the discovery of
GPIs was not achieved through a single observation, but resulted from a series of
serendipitous observations followed by an elegant set of experiments over a
number of years by leading laboratories in their respective fi elds. Highlights are
that the sugar part of the GPI is attached to the C-terminal end of a protein via
α
1 - 2Man
α
1 - 6Man
α
