Lipids covalent links with proteins

Fig. 1. Structures of lipids covalently attached to proteins. Panel A shows proteins that are lipidated on cytoplasmi-cally exposed amino acids, whereas panel B shows lipidated proteins in the extracellular leaflet. (A) iV-myristoyl glycine, palmitate thioester-linked to cysteine, farnesyl, or geranylgeranyl (prenyl) thioether-linked to cysteine. (B) A/-palmitoyl cysteine, cholesterol ester-linked to glycine, and a minimal GPI anchor linked to the to amino acid in a GPI-anchored protein. The GPI structure is shown with a diacylglycerol moiety containing two ester-linked fatty acids. Other GPI anchors are based on ceramide, while yet others have monoacylglycerol, a fatty acid ether-linked to glycerol, and/or a fatty acid ester-linked to inositol.

Resistance against ascites tumour development and interferon-inducing activity has been demonstrated in the lipopolysaccharide derived from the protein-lipopolysaccharide complex of Pseudomonas aeruginosa Both the lipid A portion and the covalently linked polysaccharide-protein complex appear to be necessary for inhibition of tumour development, whereas the lipid A with amide-linked fatty acid is suficient to induce the in vitro formation of interferon. The lipopolysaccharide of P. aeruginosa has a more pronounced effect as immunogen, mitogen, and interferon inducer than the lipopolysaccharide of Brucella melitensis, although they have similar toxicity levels. Since lipid A is responsible for most of these activities, the variations may be partially explained by structural differences in the lipopolysaccharides. 

Certain proteins are found to be covalently linked to lipid molecules. For many of these proteins, covalent attachment of lipid is required for association with a membrane. The lipid moieties can insert into the membrane bilayer, effectively anchoring their linked proteins to the membrane. Some proteins with covalently linked lipid normally behave as soluble proteins others are integral... 

Lipid-protein interactions are of major importance in the structural and dynamic properties of biological membranes. Fluorescent probes can provide much information on these interactions. For example, van Paridon et al.a) used a synthetic derivative of phosphatidylinositol (PI) with a ris-parinaric acid (see formula in Figure 8.4) covalently linked on the sn-2 position for probing phospholipid vesicles and biological membranes. The emission anisotropy decays of this 2-parinaroyl-phosphatidylinositol (PPI) probe incorporated into vesicles consisting of phosphatidylcholine (PC) (with a fraction of 5 mol % of PI) and into acetylcholine receptor rich membranes from Torpedo marmorata are shown in Figure B8.3.1. 

One of the most rapidly advancing areas in biochemistry is that concerned with the structure and metabolism of oligosaccharides that are covalently attached to proteins (in glycoproteins) and lipids (in glycolipids). The carbohydrates in these complexes vary in composition, in the way they are linked, their branching patterns and in the sugars that terminate each branch. 

In the photosynthetic and mitochondrial membranes the components of the transmembrane electron transport chain are not linked with covalent bonds, but fixed in a protein matrix. An example of such an arrangement of the electron transport chain in an artificial system can be found in papers by Tabushi et al. [244, 245], which deal with the dark electron transfer across the lipid membranes containing the dimers of cytochrome c3 from Desulfovibrio vulgaris. The dimer size is about 60 A, i.e. it somewhat exceeds the membrane thickness. This enables electron to move across the membrane via the cytochrome along the chain of hem fragments embedded in the protein. However, the characteristic time of the transmembrane electron transfer by this method is rather long (about 10 s). 

Radicals generated during peroxidation of lipids and proteins show reactivity similar to that of the hydroxyl radical however, their oxidative potentials are lower. It is assumed that the reactive alkoxyl radicals rather than the peroxyl radicals play a part in protein fragmentation secondary to lipid peroxidation process, or protein exposure to organic hydroperoxides (DIO). Reaction of lipid radicals produces protein-lipid covalent bonds and dityrosyl cross-links. Such cross-links were, for example, found in dimerization of Ca2+-ATPase from skeletal muscle sarcoplasmic reticulum. The reaction was carried out in vitro by treatment of sarcoplasmic reticulum membranes with an azo-initiator, 2,2/-azobis(2-amidinopropane) dihydrochloride (AAPH), which generated peroxyl and alkoxyl radicals (V9). 

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