In GPI anchoring, what is the nature of the bond between the protein and the lipid?
Glycosylphosphatidylinositol anchoring provides mode of attaching otherwise soluble proteins to extracellular face of plasma membrane. Biosynthesis in endoplasmic reticulum assembles GPI precursor containing phosphatidylinositol with two acyl chains inserted in lumenal leaflet, glucosamine, three mannoses and phosphoethanolamine moieties. Transamidase complex cleaves C-terminal GPI signal peptide at omega site and forms amide bond between new C-terminal carboxyl and amine of terminal ethanolamine phosphate which is glycosidically linked to mannose alpha1-2-mannose core. Further glycosidic bonds connect mannoses and glucosamine to inositol ring, while inositol joined via phosphodiester to diacylglycerol lipid. Therefore ultimate protein-lipid connection traverses ethanolamine phosphate amide plus multiple glycosidic bonds between sugars and phosphodiester between glycan and lipid. Textbooks summarizing linkage between protein and lipid as glycosidic bond referring to glycan bridge are appropriate, distinct from amide bond only of myristoylation, thioether of prenylation or ester typical of bacterial lipoproteins. This architecture places protein in outer leaflet lipid rafts modifiable by phospholipases.
Ref: Kinoshita, J Lipid Res 2020, GPI anchor structure; Fujita & Kinoshita 2012.