Myristoyl group

The myristoyl moiety attached to VP4 is observed in the poliovirus structures. This moiety is in close association with the cylinder formed by VP3 [19]. In HRVs, density consistent with the myristoyl moiety is also seen near the P cylinder [25]. In the HRVs, structural disorder of the first 25-28 N-terminal residues of VP4 obscures the connection between VP4 and the myristoyl group. The addition of myristic acid to protein is seen in many viral and cellular... 

Acylation and prenylation. The amino terminus (usually glycine) of the a subunit of any G protein is nearly always converted to an N-myristoyl group.220-223 This modification occurs in a cotranslational process after removal of the initiating methionine (Chapter 29) and can be described as an acyl transfer from coenzyme A.224 The C termini of the y subunits of heterotrimeric G proteins, and also of the monomeric proteins of the Ras family, also undergo processing. For example, the C-terminal end of an intact Ras protein contains 18 residues which probably assume a largely a-helical conformation. A cysteine side chain near the terminus and having the sequence CAAX is... 

An example is provided by actin, which contains acetyl-Met-Asp, acetyl-Met-Gln or acetyl-Met-Cys-Asp at the N terminus immediately after synthesis. Then, within 15 min the acetyl-Met is cleaved off, and the next terminal residue is acetylated.548 N-Acylation of nascent peptides by fatty acyl groups can also occur cotranslationally. For example, 14-carbon myristoyl groups are added in amide linkage to the N-terminal glycines of many cellular and virally encoded proteins.535 549 550 This may take place on the ribosomes,551... 

Tanaka, T., Ames, J. B., Harvey, T. S., Stryer, L., and Ikura, M. (1995). Sequestration of the membrane-targeting myristoyl group of recoverin in the calcium-free state. Nature 376, 444—447. 

Three major types of lipid modification can occur (1) palmitoylation, by the addition of the saturated 16-carbon fatty acyl group, palmitoyl (2) myristoylation, by the addition of the related 14-carbon myristoyl group and (3) isoprenylation, by the addition of either a 15-carbon farnesyl or a 20-carbon geranylgeranyl moiety. Any of these modifications will increase the lipophilicity of the protein and is expected to lead to membrane targeting. 

Fig. 10.2-10 Total synthesis of HIV-1 matrix protein with an N-terminal myristoyl group.

Many membrane proteins contain a covalently attached lipid group that interacts hydrophobically with lipids in the membrane. Palmitoyl groups (C16) are often attached to plasma membrane proteins, and the myristoyl group (C14) is often attached to proteins in the lipid membranes of intracellular vesicles (see Fig. 6.14). The farnesyl (C15) or geranylgeranyl group (C20) are synthesized from the five-carbon isoprene unit (isopentenyl pyrophosphate, see Fig. 5.1 A) and are therefore called isoprenoids. These are attached in ether linkage to a specific cysteine residue of certain membrane proteins, particularly proteins involved in regulation. 

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