12.9 : Lipids as Anchors

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.

The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains the CaaX motif or CaaX box where "C"stands for cysteine, "a"stands for any aliphatic amino acid, and "X"stands for any other amino acid residue. The amino acid present at the "X"position determines whether the linkage to the protein will be the farnesyl or the geranylgeranyl linkage. If the "X"is alanine, serine, methionine, cysteine, or glutamine, then farnesyl transferase recognizes the CaaX motif and links farnesyl to the protein. On the other hand, if the "X'"is glutamic acid or leucine, then geranyl transferase type I identifies the CaaX motif and attaches geranylgeranyl to it. After prenylation, the tripeptide aaX is removed by specific proteases, and a methyltransferase methylates the resultant negatively charged cysteine residue. Methylation removes the negative charge present on the cysteine and makes it hydrophobic.

Sometimes more than one lipid anchor is used to link protein to the membrane. For example, cytoplasmic tyrosine kinase is anchored to the membrane with the help of myristic and palmitic acid. However, GPI anchored proteins usually do not need another anchor for stabilization. One end of the GPI contains the two fatty acyl groups that can be inserted into the lipid bilayer. In contrast, on the other end, the phosphoethanolamine attaches to the target proteins involved in different cell functions.