Geranylgeranyl group

FIGURE 9.19 Proteins containing the C-terminal sequence CAAX can undergo prenylation reactions that place thioether-linked farnesyl or geranylgeranyl groups at the cysteine side chain. Prenylation is accompanied by removal of the AAX peptide and methylation of the carboxyl group of the cysteine residue, which has become the C-terminal residue. 

Lipidation of proteins may involve N-terminal myristoylation,131 S-prenylation (farnesyl- and geranylgeranyl groups) of cysteine residues at or close to the C-terminus, and S-palmitoylation[31 of cysteines throughout proteins (Scheme 2). 

The following are recent reviews on the molecular and physical properties of these transferases which transfer geranylgeranyl groups to defined sites on protein substrates. 

Beyond merely anchoring a protein to the membrane, the attached lipid may have a specific role. In the plasma membrane, proteins with GPI anchors are exclusively on the outer face and are confined within clusters, as we shall see below, whereas other types of lipid-linked proteins (with farnesyl or geranylgeranyl groups attached Fig. 11-14) are exclusively on the inner face. Attachment of a specific lipid to a newly synthesized membrane protein therefore has a targeting function, directing the protein to its correct membrane location. 

Prenylation (covalent attachment of an isoprenoid see Fig. 27-30) is a common mechanism by which proteins are anchored to the inner surface of cellular membranes in mammals (see Fig. 11-14). In some of these proteins the attached lipid is the 15-carbon farnesyl group others have the 20-carbon geranylgeranyl group. Different enzymes attach the two types of lipids. It is possible that prenylation reactions target proteins to different membranes, depending on which lipid is attached. Protein prenylation is another important role for the isoprene derivatives of the pathway to cholesterol. 

The first step of the series of modifications involved in the processing of CAAX-type prenyl proteins occurs in the cytoplasm, catalyzed by either protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I (GGTase-I). The specificity for either of these two enzymes for the most part depends on the identity of the last amino acid X of the CAAX consensus sequence. When X is serine, cysteine, alanine, or glutamine, the 15 carbon farnesyl group is added to the cysteine catalyzed by FTase and when X is leucine, the 20 carbon geranylgeranyl group is added by... 

G Protein is a class of proteins, occurring at the plasma membrane, that participates in transmitting signals from the extracellular fluid to various enzymes within the cell. Myristic acid is bound to G protein. Specifically, myristic acid is attached to the a subunit of G protein. This lipid is bound via an amide linkage to the N-terminal glycine. A geranylgeranyl group is attached via a thiol-ester bond to a cysteine residue on the y subunit of G protein (Casey and Seabra, 1996). 

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