3.3. Glycophosphatidylinositol

Glycosylphosphatidylinositols (GPI) are complex structures to which the C-terminus of proteins gets attached during their post-translational modification [48]. All GPI have a core glycan structure sandwiched between an ethanolamine phosphate linker, bridging the C-terminal of the protein with the highly conserved glycan core, and a phosphatidylinositol (PI) group. The fatty acids of the PI moiety attach the GPI to the cell membrane. So far more than 200 proteins have been found to be anchored by a GPI to the cell surface and more than 20 GPI structures have been elucidated [49]. Some of the proteins attached to GPI anchor are enzymes like alkaline phosphatase (APase), acetylcholinesterase (AChE) and 5<sup>0</sup> -nucleotidase, complement defense proteins like decay accelerating factor (DAF or CD55), CD59, and mammalian antigens like Thy-1, or protozoan antigens like variant surface glycoprotein (VSG) found on the cell surface of Trypanosoma [48].

Unlike GPI-anchored proteins not much is known about biological functions of GPI anchors, apart from their role as a membrane anchor for proteins. Given the complexity and diversity of their structures, they are thought of as being involved in many different biological functions but there are not sufficient experimental evidences to draw definitive conclusions [50]. However, there are several studies implicating their involvement in sorting of proteins in the lipid raft and in signal transduction [51–53]. Other studies have shown that the structure and conformation of proteins change upon binding to GPI anchors [54, 55]. Besides this physiological role, deficiency of GPI anchors on red blood cells causes a chronic pathological disorder paroxysmal nocturnal hemoglobinuria (PNH) [56].

#### 3.4. Lipopolysaccharides

Lipopolysaccharides (LPS), also referred to as endotoxins, are a major component of the outer membrane of gram negative bacteria and are essential for maintaining the structural integrity of the membrane. LPS have three components: lipid A, core oligosaccharide and O-antigen polysaccharide. Lipid A is the active component and under normal conditions consists of β(1–6) linked glucosamine disaccharides. The diglucosamine backbone is phosphorylated and decorated with multiple fatty acids anchoring them in the outer leaflet of the bacterial cell membrane. Lipid A, when released from the cell, is recognized by pattern recognition receptor TLR4 triggering cytokine synthesis. At low level of endotoxins, the innate immune system eliminates it, but at high concentrations it can prove fatal [57].
