Thioacylated proteins

Protein acyltransferases (PATs) and thioacyl protein thioesterases (APTs). 45... 

Thioacylated proteins contain fatty acids in thioester linkage to cysteine residues [7-9] (Fig. lA). Protein thioacylation is frequently referred to as palmitoylation, although fatty acids other than palmitate are found on thioacylated proteins. Membrane proteins as well as hydrophilic proteins are thioacylated, the latter, in many cases, acquiring the modification when they become associated with a membrane compartment as a result of initial N-myristoylation or prenylation. Examples include G-protein coupled receptors, the transferrin receptor, the cation-dependent mannose-6-phosphate receptor, and hydrophilic proteins such as members of the Src family of protein tyrosine kinases (e.g., p59h " and p56 ) as well as H-Ras, N-Ras, and the synaptic vesicle protein SNAP-25. The yeast palmitoyl proteome, i.e., the collection of all S-acylated proteins in yeast, was recently defined via a comprehensive proteomics approach (A.F. Roth, 2006). It consists of 50 proteins including... 

Two thioacyl protein thioesterases (APTs) have been identified. Unlike PATs, both are soluble proteins. Acylprotein thioesterase-1 (APTl) was purified from rat liver cytosol using palmitoylated G-protein a-subunit as a substrate (J.A. Duncan, 1998, 2002). This thioesterase, a 29-kDa monomeric protein, is likely to be the one involved in turnover of cytoplasmically disposed thioacyl groups of proteins. It displays both acylprotein thioesterase activity as well as lysophospholipase activity, but thioacylproteins are by far the preferred substrates. The second acylprotein thioesterase, protein palmitoylthioesterase-1 (L.A. Camp,... 

This enzyme [EC 4.1.3.25] catalyzes the conversion of (35)-citramalyl-CoA to acetyl-CoA and pyruvate. The (35)-citramalyl thioacyl-carrier protein can also be utilized as a substrate. This enzyme has been reported to be a component of citramalate lyase [EC 4.1.3.22]. 

Thioacylation frequently dictates plasma membrane targeting of proteins lacking trans-membrane spans. In the case of p59 5 " targeting occurs directly, with the iV-myristoylated protein becoming thioacylated and plasma membrane associated rapidly upon completion of synthesis. In contrast, p56 appears to be thioacylated on intracellular membranes and arrive at the plasma membrane via vesicular transport (bound to the cytoplasmic face of secretory vesicles) (M. Bijlmakers, 1999). In yet another targeting variation, newly synthesized A-myristoylated G, a dually acylated trimeric G protein cx-subunit, associates with all cellular membranes but accumulates eventually at the plasma membrane the plasma membrane form is the only one that is both A-myristoylated and thioacylated. 

Levesque G, Arsene P, Fanneau-Bellenger V, Pham T (2000) Protein thioacylation. 1. Reagents design and synthesis. Biomacromolecules 1 387-399... 

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