thumb|525x525px|Lipid membrane with various proteins
Lipid-anchored proteins (also known as lipid-linked proteins) are proteins that are covalently attached to lipids embedded into biological membranes. The lipid-anchored protein can be located on either side of the cell membrane. Thus, the lipid serves to anchor the protein to the cell membrane. Such proteins are a type of proteolipids.
The lipid groups contribute to the intracellular localization and the biological function of the protein to which they are attached. A protein can have multiple lipid groups covalently attached to specific amino acid residues.) at cysteine residues of the protein. More specifically, these isoprenoid groups, usually farnesyl (15-carbon) and geranylgeranyl (20-carbon) are attached to the protein via thioether linkages at cysteine residues near the C terminal of the protein. This prenylation of lipid chains to proteins facilitate their interaction with the cell membrane.
Roles and function
thumb|Prenylation chains (e.g. [[geranyl pyrophosphate)]]
Prenylated proteins are particularly important for eukaryotic cell growth, differentiation and morphology. More specifically, Ras is the protein that undergoes prenylation via farnesyltransferase and when it is switched on it can turn on genes involved in cell growth and differentiation. Thus overactiving Ras signalling can lead to cancer. An understanding of these prenylated proteins and their mechanisms have been important for the drug development efforts in combating cancer. Other prenylated proteins include members of the Rab and Rho families as well as lamins. The most common fatty acids that are covalently attached to the protein are the saturated myristic (14-carbon) acid and palmitic acid (16-carbon). Proteins can be modified to contain either one or both of these fatty acids. in which the myrisitc acid is attached to the α-amino group of an N-terminal glycine residue through an amide linkage. Other proteins that are myristoylated and involved in the regulation of apoptosis are actin and gelsolin.
S-palmitoylation
thumb|292x292px|Palmitoylation
S-palmitoylation (i.e. attachment of palmitic acid) is a reversible protein modification in which a palmitic acid is attached to a specific cysteine residue via thioester linkage. An example in which palmitoylation of a protein plays a role in cell signaling pathways is in the clustering of proteins in the synapse. When the postsynaptic density protein 95 (PSD-95) is palmitoylated, it is restricted to the membrane and allows it to bind to and cluster ion channels in the postsynaptic membrane. Thus, palmitoylation can play a role in the regulation of neurotransmitter release.
Palmitoylation mediates the affinity of a protein for lipid rafts and facilitates the clustering of proteins. The clustering can increase the proximity of two molecules. Alternatively, clustering can sequester a protein away from a substrate. For example, palmitoylation of phospholipase D (PLD) sequesters the enzyme away from its substrate phosphatidylcholine. When cholesterol levels decrease or PIP2 levels increase the palmitate mediated localization is disrupted, the enzyme trafficks to PIP2 where it encounters its substrate and is active by substrate presentation.
GPI proteins
thumb|490x490px|Structure of the glycophosphatidylinositol anchor in the plasma membrane of a eukaryotic cell
Glycosylphosphatidylinositol-anchored proteins (GPI-anchored proteins) are attached to a GPI complex molecular group via an amide linkage to the protein's C-terminal carboxyl group. This GPI complex consists of several main components that are all interconnected: a phosphoethanolamine, a linear tetrasaccharide (composed of three mannose and a glucosaminyl) and a phosphatidylinositol. The phosphatidylinositol group is glycosidically linked to the non-N-acetylated glucosamine of the tetrasaccharide. A phosphodiester bond is then formed between the mannose at the nonreducing end (of the tetrasaccaride) and the phosphoethanolamine. The phosphoethanolamine is then amide linked to the C-terminal of the carboxyl group of the respective protein. These proteins are only located on the exterior surface of the plasma membrane. Furthermore, GPI proteins play an important in embryogenesis, development, neurogenesis, the immune system and fertilization. Other roles that GPI modification allows for is in the association with membrane microdomains, transient homodimerization or in apical sorting in polarized cells.