Structure, biosynthesis, and function of glycosylphosphatidylinositols

Abstract

The last few years have witnessed an explosion in our knowledge of GPI membrane anchors and related glycolipids and molecules where structure details are available, as illustrated in Figure 2. There is now sufficient information on a handful of these molecules to allow a detailed comparison of their chemical structures. Despite a common structural theme, i.e., the presence of mannoglucosaminyl-PI, a great deal of diversity exists in both the glycan structures and the glycerol-linked aliphatic substituents. The complexities of the structures clearly show that a multitechnique approach is required in the elucidation of their structures. The anticipated publication of more structures from a wider range of organisms may reveal even greater diversity, as well as suggesting possible biosynthetic pathways. The details of a potential biosynthetic pathway in T. brucei are becoming apparent, but confirmation of its importance awaits the isolation and characterization of the enzymes involved. Leishmania, in which LPG, GPIs, GIPLs, and GPI membrane anchors are produced, may also provide an interesting system for biosynthetic studies. The recent description of a GPI biosynthetic system in yeast may provide the crucial breakthroughs necessary in unraveling the enzymes and sugar donors involved in the biosynthetic pathway and possibly the role of the GPI membrane anchor in the function of proteins containing these moieties. Knowledge of the solution structure (conformation), in addition to the complete chemical structure, of the T. brucei VSG anchor has led to speculation that the glycan fulfills a space-filling role in the VSG coat. Many other possible roles of GPI membrane anchors have been suggested, including the shedding and turnover of membrane proteins, signal transduction, and intracellular targeting. Nevertheless, the only function of GPIs that we can so far be certain of is that they anchor proteins or polysaccharide to a membrane. Regardless of the roles GPIs may or may not ultimately be shown to play, the fact that such a widely occurring structure has only recently been characterized serves as a reminder of the incompleteness of our knowledge of biological phenomena and the constant possibility of finding novel molecules in obvious places.