Glypiation
Glypiation is the addition by covalent bonding of a glycosylphosphatidylinositol anchor and is a common post-translational modification that localizes proteins to cell membranes. This special kind of glycosylation is widely detected on surface glycoproteins in eukaryotes and some Archaea.
GPI anchors consist of a phosphoethanolamine linker that binds to the C-terminus of target proteins. Glycan's core structure has a phospholipid tail that anchors the structure to the membrane.
Both the lipid moiety of the tail and the sugar residues in the glycan core have considerable variation, demonstrating vast functional diversity that includes signal transduction, cell adhesion and immune recognition. GPI anchors can also be cleaved by enzymes such as phospholipase C to regulate the localization of proteins that are anchored at the plasma membrane.
Mechanism
Similar to the precursor glycan used for N-glycosylation, GPI anchor biosynthesis begins on the cytoplasmic leaflet of the ER and is completed on the luminal side. During this process, 3-4 Man and various other sugars are built onto a phosphatidylinositol molecule embedded in the membrane using sugars donated from sugar nucleotides and dolichol-P-mannose outside and inside the ER, respectively. Additionally, 2-3 phosphoethanolamine linker residues are donated from phosphatidylethanolamine in the ER lumen to facilitate binding of the anchor to proteins.Proteins destined to be glypiated have two signal sequences:
- An N-terminal signal sequence that directs co-translational transport into the ER
- A C-terminal signal sequence that is recognized by a GPI transamidase