Eukaryotic signal peptidases

The signal sequence is proteoly tically cleaved by signal pepetidase (member enzyme of translocon) once protein is translocated. The eukaryotic signal peptidases have multiple catalytic subunits with broad substrate specificity. The enzyme generally cleaves at a site that has small aliphatic residues at position -1 and -3. On-line prediction of signal peptide and cleavage site is available at PrediSi (http //www.predisi.de). 

Ijalsma, H. et al (1998) Functional analysis of the secretory precursor processing machinery of Bacillus subtilis . identification of a eubacterial homolog of archaeal and eukaryotic signal peptidases. Genes Dev., 12 (15), 2318-2331. 

In addition to the destructive proteolysis processes in the proteasome and lysosome, many constructive proteolysis processes occur in cells. In both prokaryotes and eukaryotes, secreted proteins contain a signal peptide at the N-terminus that directs them to the secretary pathway. This signal peptide must be cleaved later by signal peptidases (typically serine proteases)... 

The signal hypothesis postulates the existence of several proteins necessary for secretion. These include the components of the SRP, which is proposed to bind to the signal sequence and block further translation of the mRNA coding for the mature protein SRP receptor, or docking protein, which relieves the translation block imposed by the SRP ribophorins, which bind the ribosome to the ER membrane signal peptidase and signal-peptide peptidase, discussed above and other proteins, which form a pore or transport apparatus in the membrane. Some of these proteins, the SRP, SRP receptor, signal peptidase, and ribophorins, have been isolated from eukaryotic cell extracts and characterized. 

The genetic evidence presented above makes it clear that E. coli, and possibly other bacteria, possess a complex set of proteins that act in the protein-secretion process. Although it appears that at least one protein, the M13 phage coat protein, can be localized and processed in the absence of proteins other than signal peptidase (Section V,B) (Silver et al., 1981 Ohno-Iwashita and Wickner, 1983 Watts et al., 1981), most proteins of the bacterial cell envelope require the participation of a secretion apparatus for proper localization. Whether the bacterial secretion process is analogous to the eukaryotic process remains to be seen. The recent development of in vitro translocation systems derived from E. coli should facilitate research in this area (Rhoads et al., 1984 Muller and Blobel, 1984b). 

In eukaryotic systems, secretion of a protein across the ER requires the presence of a functional signal sequence and participation of SRP, the membrane and associated as yet undefined export apparatus, the SRP receptor, and a signal peptidase. Biochemical evidence derived from experiments in in vitro translocation systems generally supports the signal hypothesis (see Section II,C). 

The mechanism for translocating bacterial proteins across the Inner membrane shares several key features with the translocation of proteins into the ER of eukaryotic cells. First, translocated proteins usually contain an N-termlnal hydrophobic signal sequence, which is cleaved by a signal peptidase. Second, bacterial proteins pass through the Inner membrane In a channel, or translocon, composed of proteins that are structurally similar to the eukaryotic Sec61 complex. Third, bacterial cells express two proteins, Ffh and its receptor (FtsY), that are homologs of the SRP and SRP receptor, respectively. In bacteria, however, these latter proteins appear to function mainly In the insertion of hydrophobic membrane proteins Into the Inner membrane. Indeed, all bacterial proteins that are translocated across the inner membrane do so only after their synthesis In the cytosol is completed but before they are folded Into their final conformation. 

Dalbey, R. E., and G. Von Heijne. 1992. Signal peptidases in prokaryotes and eukaryotes a new protease family. Trends Biochem. Sci. 17 474-478. 

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