Cysteine lipidated

Reulen, S.W.A., Brusselaars, W.W.T., Langereis, S., Mulder, W.J.M., Breurken, M., and Merkx, M. (2007) Protein-liposome conjugates using cysteine-lipids and native chemical ligation. Bioconjugate Chem. 18(2), 590-596. 

Palmitoylation is the post-translational lipid modification of cysteine-residues in a variety of proteins. 

Many GPCRs contain one or more conserved cysteine residues within their C-terminal tails, which are modified by covalent attachment of palmitoyl or isoprenyl residues. The palmitoyl moiety is anchored in the lipid bilayer forming a fourth intracellular loop. There is evidence that palmitoylation of a GPCR is a dynamic process and may affect receptor desensitization. 

Primary and secondary products, and end-products of lipid peroxidation have all been shown to accumulate in senile cataracts (Babizhayev, 1989b Simonelli et al., 1989). Accumulation of these compounds in the lenticular epithelial membranes is a possible cause of damage preceding cataract formation. In senile cataracts there is also extensive oxidation of protein methionine and cysteine in both the membrane and cytosol components (Garner and Spector, 1980), while in aged normal lenses a lesser extent of oxidation was confined to the membrane. The authors therefore suggested that oxidation of membrane components was a precataract state. 

Despite the conclusions in the cited literature about direct MT interaction with free radicals, the mechanism of MT antioxidant activity remains obscure. Markant and Pallauf [339] concluded that cysteine groups and not zinc are responsible for the inhibition of lipid peroxidation in hepatocytes. Maret and Vallee [340,341] also questioned the possibility of direct scavenging of free radicals by MT and suggested that zinc release is a major mechanism of antioxidant effects of metallothioneins. 

A major scaffolding protein of the PSD is PSD95. Two N-terminal cysteines of this protein bind palmitic acid residues, which anchor PSD95 to lipid rafts [30], PSD95 contains several domains that bind other proteins three so-called PDZ domains (short for PSD95/disc large/zona occludens-1), a src homology (SH3) domain, and a gua-nylate kinase (GK) domain. This family of proteins are... 

A first approach to study the interaction of posttranslational modified Ras proteins with membranes was the analysis of binding and exchange of isoprenyl-ated peptides with and between lipid vesicles utilizing a fluorescent bimanyl label. Studies with K-Ras peptides revealed that a single isoprenyl group is sufficient for membrane association only if supported by carboxymethylation of the C-terminal cysteine [227,228]. 

Fig. 19. Lipopeptides with the aminoacid sequence of the Ras C-terminus and the natural or artificial lipid-modifications can be coupled with C-terminally truncated Ras via a maleimi-docaproyl linker. This electrophile reacts with free thiol groups (here, a C-terminal cysteine at the Ras moiety)...

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). 

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