geranylgeranylation

Geranylgeranylation is a form of prenylation, which is a post-translational modification of proteins that involves the attachment of one or two 20-carbon lipophilic geranylgeranyl isoprenoid units from geranylgeranyl diphosphate to one or two cysteine residue(s) at the C-terminus of specific proteins. Prenylation (including geranylgeranylation) is thought to function, at least in part, as a membrane anchor for proteins.{{cite journal|last1 = Jiang|first1 = Yu|last2 = Proteau|first2 = Philip|last3 = Poulter|first3 = Dale|last4 = Ferro-Novick|first4 = Susan|authorlink4=Susan Ferro-Novick |year = 1995|title = BTS1 Encodes a Geranylgeranyl Diphosphate Synthase in Saccharomyces cerevisiae|journal = Journal of Biological Chemistry|volume = 270|issue = 37|pages = 21793–21799|doi = 10.1074/jbc.270.37.21793|pmid = 7665600|doi-access = free}}

The process of geranylgeranylation can be catalyzed by either geranylgeranyl transferase I (GGTase I) or Rab GGTase (also GGTase II). GGTase I catalyzes the addition of one geranylgeranyl group onto the C-terminal consensus sequence CAAL (somewhat similar to farnesyltransferase reactions), where C=cysteine, A=any aliphatic amino acid, and L=leucine. Rab GGTase adds a total of two geranylgeranyl groups onto two cysteine residues at the C-terminal consensus sequence CXC or XXCC. The source of the geranylgeranyl group is geranylgeranyl diphosphate, which is synthesized by GGPS1 within the isoprenoid biosynthetic pathway.{{cite journal|last1 = Wiemer|first1 = Andrew J.|last2 = Hohl|first2 = Raymond J.|last3 = Wiemer|first3 = David F.|title = The intermediate enzymes of isoprenoid metabolism as anticancer targets|journal = Anti-Cancer Agents in Medicinal Chemistry|year = 2009|volume = 9|issue = 5|pages = 526–542|pmid = 19519294|doi = 10.2174/187152009788451860}}

An example of this can be seen in the lipid anchoring of the Rho GTPase family of signaling molecules and the gamma subunit of heterotrimeric G proteins.