Lipidation

Lipid-anchored proteins (also known as lipid-linked proteins) are proteins located on the surface of the cell membrane that are covalently attached to lipids embedded within the cell membrane. These proteins insert and assume a place in the bilayer structure of the membrane alongside the similar fatty acid tails. 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.

The lipid groups plays a role in protein interaction and can contribute to the function of the protein to which it is attached. Furthermore, the lipid serves as a mediator of membrane associations or as a determinant for specific protein-protein interactions. For example, lipid groups can play an important role in increasing molecular hydrophobicity. This allows for the interaction of proteins with cellular membranes and protein domains.

Overall, there are three main types of lipid-anchored proteins which include prenylated proteins, fatty acylated proteins and glycosylphosphatidylinositol-linked proteins (GPI). A protein can have multiple lipid groups covalently attached to it, but the site where the lipid binds to the protein depends both on the lipid group and protein.

As the name suggests, prenylated proteins are proteins with covalently attached hydrophobic isoprene polymers (i.e. branched five-carbon hydrocarbon) 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.

The prenylation motif “CAAX box” is the most common prenylation site in proteins, that is, the site where farnesyl or geranylgeranyl covalently attach. In the CAAX box sequence, the C represents the cysteine that is prenylated, the A’s represent any aliphatic amino acid and the X determines the type of prenylation that will occur. If the X is an Ala, Met, Ser or Gln the protein will be farnesylated via the farnesyltransferase enzyme and if the X is a Leu then the protein will be geranylgeranylated via the geranylgeranyltransferase I enzyme. Both of these enzymes are similar with each containing two subunits.

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Wikipedia