Mehlert, A. Mol Biochem Parasitol. Ralton, J. Precursors from different pathways are assembled on distinct pools of phosphatidylinositol and undergo fatty acid remodeling. J Biol Chem. Vidugiriene, J. Hilley, J. Mol Biol Cell. Kinoshita, T. J Biochem Tokyo.
CrossRef Google Scholar. Smith, T. EMBO J. Descoteaux, A. Biochim Biophys Acta. Ali, S. Biochem J. Lipardi, C. Nosjean, O.
Protein Eng. Cell — GPI-APs have very diverse functions in various cells across species. The glycosyltransferase superfamily is composed of 26 subfamilies in humans, including for example the UDP gluccuronosyltransferase family, members of which are responsible for hepatic bilirubin metabolism , and the glycogen phosphorylases. Extracellular release of the glycosylphosphatidylinositol GPI -linked Leishmania surface metalloprotease, gp63, is independent of GPI phopholipolysis: implications for parasite virulence.
Roux, B. McGwire, G. Benting, J.
In particular in the parasitic protozoal parasites, lipophosphoglycans are present in a glycocalyx that covers the external cell surface, where they are intimately involved in host-pathogen interactions. The lipophosphoglycans of Leishmania species, the causative agent of leishmaniases and an intracellular parasite of macrophages transmitted to humans via the bite of its sand fly vector, have received intensive study. However, all of the surface-bound molecules of the Trypanosomatid family have a common structural feature in that they contain a highly conserved GPI-anchor motif that differs significantly from those in mammalian cells.
In most trypanosomatids, the glycocalyx is composed mainly of GPI-anchored glycoproteins, but in that of the Leishmania promastigote stage GPI-anchored phosphoglycosylated glycans predominate. The lipid component is a monoalkyl-lysophosphatidylinositol with saturated C 24 to C 26 alkyl groups. These lipophosphoglycans are essential for successful invasion of the host animal.
In addition, the galactofuranose unit Gal f , which does not occur in mammalian cells, is believed to play a part in the pathogenicity. Low-molecular-weight free glycosylinositol phospholipids occur in the organisms also with a glycan core that is similar structurally to that of the glycan core of the lipophosphoglycan or to that of the GPI-anchored glycoprotein. The protozoan parasite Toxoplasma gondii expresses non-protein-linked GPI, which are highly immunogenic. Analogous lipophosphoglycans with the lipid backbone consisting of a ceramide, i. Phosphatidylinositol mannosides: These are related lipids with the first mannose residue attached to the 2-hydroxyl group and the second to the 6-hydroxyl of myo -inositol that are found uniquely in the cell walls of the bacterial suborder Corynebacterineae , which include Mycobacteria and related species, many of which are important pathogens.
They are present in both the inner and outer membranes of the cell envelope of the organisms. For example, in Mycobacteria sp. Phosphatidylinositol mannosides range in structure from simple mono-mannosides in some Streptomyces and Mycobacterium species and in Propionibacteria to molecules with 80 or more hexose units. They are important structural components of membranes with functions in cell wall integrity, permeability and division.
The phosphatidylinositol dimannoside from M. This is the basic structure from which additional phosphatidylinositol mannosides are produced, and with two further acylations designated Ac 2 PIM 2 it is the major lipid component of the inner leaflet of the inner membrane.
Similarly, forms with up to four further mannose units are present, and a hexamannoside Ac 2 PIM 6 especially on the outer leaflet of the inner membrane is often a major component. Biosynthesis of such complex lipids involves a number of reactions, and it is apparent that the first two mannosylation steps of the pathway occur on the cytoplasmic face of the plasma membrane by the action of two distinct phosphatidylinositol mannosyltransferases; the additional acylations also occur on this membrane.
On the other hand, further mannosylations require first a transfer to the periplasmic side of the membrane and then the action of integral membrane-bound glycosyltransferases, but many of these enzymes have yet to be identified. It is evident that these lipids modulate the inflammatory and immune system responses in host animals in many different ways. Trehalose-containing lipids from these species are discussed on a separate web page.
Lipomannans from Mycobacteria sp.
go to link For example, in M. The phosphatidylinositol tetramannosides Ac 1 PIM 4 and Ac 2 PIM 4 appear to be the intermediates at the branch point in the biosynthesis of the phosphatidylinositol hexamannosides and of lipomannans and lipoarabinomannans. Such molecules are believed be important for the structural integrity of the cell walls of the organisms, a function similar to that of the lipoteichoic acids.
They have been implicated in host—pathogen interactions in tuberculosis and leprosy. In infected animals, these lipopolysaccharides interact with different receptors and exert potent anti-inflammatory effects, which may assist in repressing the host innate immune system.
In particular, lipoarabinomannan binding to lactosylceramide in lipid rafts is essential for the phagocytosis of mycobacteria by human neutrophils. It is hoped that knowledge of the biosynthetic enzymes may lead to improved drug therapies. Related Lipids: Bacteria of the genus Thermomicrobia contain unusual long-chain 1,2-diol-containing phosphoinositides and inositolmannosides in which the stereochemistry of the diol unit is the same as the corresponding positions in sn -glycerolphosphate.
C 17 to C 23 Straight-and branched-chain saturated fatty acids are linked to position 2 of the diol. Structure and Occurrence of Glycosylphosphatidylinositol-Anchored Proteins As studies were extended to mammalian systems, it soon became apparent that there was a basic general structure for the lipid component of what became known as the glycosylphosphatidylinositol GPI -anchored proteins. Biosynthesis and Function of GPI-Protein Complexes Considerable progress has been made towards and understanding of the biosynthesis of GPI-protein complexes, and it is apparent that both the biosynthesis of GPI precursors and post-translational modification of proteins with GPI take place in the endoplasmic reticulum and Golgi.
Lipophosphoglycans and Phosphatidylinositol Mannosides Lipophosphoglycans: In addition to the GPI-anchor molecules, carbohydrates attached to phosphatidylinositols play a role in the surface antigenicity both of protozoal parasites, such as the Trypanosomatid family, and of prokaryotic organisms, such as actinomycetes or coryneform bacteria. Recommended Reading Abrahams, K. Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target. Forestier, C.
Leishmania lipophosphoglycan: how to establish structure-activity relationships for this highly complex and multifunctional glycoconjugate? Fujihara, Y. GPI-AP release in cellular, developmental, and reproductive biology. Lipid Res. Heider, S.
Biomedical applications of glycosylphosphatidylinositol-anchored proteins. Kinoshita, T. Komath, S. Generating anchors only to lose them: the unusual story of glycosylphosphatidylinositol anchor biosynthesis and remodeling in yeast and fungi. Levental, I. Greasing their way: lipid modifications determine protein association with membrane rafts.
Glycosylphosphatidylinositol (GPI) Anchoring of Proteins, Volume 26 (The Enzymes): Medicine & Health Science Books @ hartbaslisickhtac.tk Editorial Reviews. About the Author. Fuyu Tamanoi is a biochemist who has served on the Glycosylphosphatidylinositol (GPI) Anchoring of Proteins (The Enzymes Book 26) - Kindle edition by Anant Kumar Menon, Taroh Kinoshita, Peter A.