Consensus sequences, signal peptides

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

Fig. 7. Consensus sequences of the signal peptides of (a) the three Ca2+-sensitive caseins and (b) the K-caseins, taken from sequences for the cow, sheep, man, guinea pig, rat, mouse, and rabbit.

Austen et al. (1984) found that the consensus signal peptide inhibits protein translocation into RER microsomes. Synthetic preproparathyroid hormone signal sequence also decreased the translocation and processing of four prehormones in a cell-free translation system (Majzoub et al., 1980). Synthesis of the prehormones appears to be unaffected. Addition of a control peptide failed to inhibit processing. 

Two peptide sequences are necessary for GPI anchor addition, an N-terminal signal peptide directing the nascent protein into the endoplasmic reticulum and a C-terminal signal peptide directing GPI anchor attachment. The signal for GPI anchor attachment has been localized to the C-terminal region of GPI-linked proteins [101-103]. Yet, comparison of cDNA deduced amino acid sequences of C-terminal regions from GPI-anchored proteins does not identify a clear consensus sequence [5,104—106]. 

---