12.9:
Lipids as Anchors
The three most common types of lipid anchors are prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI anchors.
The prenyl groups are the 15 carbon farnesyl and the 20 carbon geranylgeranyl groups. They bond to cysteine residues at or near the carboxy terminus of proteins.
Saturated 14 carbon myristic acid and the 16 carbon palmitic acid are the most common fatty acyl anchors linked to proteins.
The addition of myristic acid, or myristoylation, happens at a protein's N-terminal glycine residue. Palmitoylation of the proteins can occur at the N- or C- terminal cysteine residue.
Prenylated, myristoylated, and palmitoylated proteins play an essential role in intracellular signaling pathways and protein-protein interactions.
GPI anchors attach to extracellular proteins and contain a core structure of phosphatidylinositol, glucosamine, three mannoses, and phosphoethanolamine.
The phosphoethanolamine bonds to the C-terminal amino acid of the target protein, and the phospholipid inserts itself into the outer layer of the membrane.
This allows GPI anchored proteins to participate in extracellular functions such as cell-cell communication and cell adhesion.
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.