Biology Reference
In-Depth Information
O
H
PROTEIN
C
N
phosphoethanolamine
glycan
glucosamine
O
OH
O
O
P
PI
OH
HO HO
O
--
OH
membrane
interior
PI head group
GPI ANCHORED PROTEIN
FIGURE 6.13
Cartoon drawing depicting a typical GPI-anchored protein.
attached to the exo-cytoplasmic (outer leaflet) surface, while the others are lipid-anchored to
the endo-cytoplasmic inner leaflet surface of cells. Since lipid anchors by themselves are very
weak, these proteins are often additionally attached by other, usual interactions (electrostatic
and hydrophobic).
The 14-carbon saturated fatty acid,
myristic acid (14:0), is often employed as a lipid anchor for proteins
[29]
. This may
seem an odd choice since myristic acid, in sharp contrast to the other commonly employed
fatty acid lipid anchor palmitic acid (16:0), is found in membranes only at very low levels.
Myristoylation was first reported in 1982 for the proteins calcineurin B
[30]
and the cata-
lytic subunit of the cyclic AMP-dependent protein kinase
[31]
. Myristic acid was found to
be acylated to the anchored protein via an amide linkage to an N-terminal glycine
(
Figure 6.10
). This linkage is found only in eukaryotes and viral proteins and is established
early in translation. Generally, it is an irreversible protein modification. Additional
anchoring for myristoylated proteins is provided by electrostatic interactions between posi-
tively charged protein side chains and negatively charged membrane phospholipids. Some
N-myristoylated proteins undergo additional fatty acyl modifications by attachment of
palmitoyl groups to cysteines via reversible thio esters. An example of these dually
acylated proteins include members of the Src family of tyrosine kinases (eg. Fyn, Lck).
N-Myristoylated proteins have a variety of important functions including roles in several
signal transduction cascades. Under unusual circumstances where myristic acid is limiting,
some other fatty acids including shorter-chain and unsaturated, can be attached to the
N-terminal glycine.
1. MYRISTOYLATED LIPID-ANCHORED PROTEINS
