A comprehensive review of signal peptides: Structure, roles ...

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Discovery of signal peptides

In 1971, for the first time, Gunter Blobel and David Sabatini hypothesized the presence of intrinsic information for translocation of protein into the membrane (Blobel and Sabatini, 1971). In 1972, Milstein and his co-workers reported that the light chain of IgG becomes mature in the endoplasmic reticulum vesicles in myeloma cell (Milstein et al., 1972). This process takes place by cleaving the amino-terminal of nascent IgG. In 1975, Blobel postulated that proteins transferring to different

Applications and importance of signal peptides

Day by day, the demand for biotherapeutics and recombinant proteins is increasing. Hence, several prokaryotic and eukaryotic hosts have been widely accepted for cytoplasmic expression of recombinant protein. However, there are several obstacles in the large-scale production of recombinant proteins, among which inclusion body formation and protein degradation via proteases are the important factors. On the other hand, endogenous proteins may interfere with the folding of a recombinant secretory

Secretory systems in prokaryotes and eukaryotes

Several different secretory pathways have evolved among organisms: 1) to come up with the secretory needs of rapidly growing organisms such as bacteria and yeasts, 2) to offset the low rate of protein synthesis versus the high rate of secretion, and 3) to be able to secrete proteins with different characteristics. Additionally, the type of secretory pathway, which is determined by the SP’s features, affects protein localization in the cell as well as post/co-translational modification of

Signal peptide structure

A typical SP has 25–30 residues (von Heijne, 1990a). Longer SPs (up to ∼140 residues) are usually found in eukaryotes; however, they have been also observed in viral proteins and bacterial autotransporters (Hiss and Schneider, 2009; Szabady et al., 2005). Long eukaryotic SPs are mainly organelle-targeting sequences. Longer SPs mostly remain stable after protein maturation and add extra functions to protein targeting (Hiss and Schneider, 2009). Tat SPs are longer than the Sec or SRP SPs; they

Types of signal peptides

The majority of SPs that are transported via Sec/Tat/SRP pathways in all life domains have a tripartite structure sharing general similarities as described in the previous sections. Although SPs could be expressed in heterologous hosts (Kober et al., 2013), they are not always recognized by the translocons from other species (Kim et al., 2002). On the other hand, the secretory machinery of a heterologous host might recognize the foreign SP, although secretion might not be as efficient as the

SPase role and classification

Protein export is accompanied by SP cleavage, although it is not always necessary for protein translocation. Human cytomegalovirus SP (US2) and cyclophilin SP from the cattle parasite are two examples bearing a non-cleavable SP in spite of the −3, −1 motif presence (Rusch and Kendall, 2007; Gewurz et al., 2002; Ebel et al., 2004). Interestingly, SPases are not only responsible for the cleavage of SPs, but they indeed catalyze the final steps in protein maturation (Rusch and Kendall, 2007). In

Limitation of signal peptide application

SPs represent a promising role in recombinant protein production, whereas one should tackle several hindrances to reach the best performance of SPs. Talking about E. coli as one of the most encouraging biological production systems, a major obstacle shows up. Recombinant proteins harboring SP mostly pass through the inner membrane of E. coli; however, passage through both membranes is somewhat impossible (Mergulhao et al., 2005). There are few studies denoting complete excretion of recombinant

Conflict of interest

Authors declare no conflict of interests.

Acknowledgment

This study was supported by Grant no. 13435 from the Research Council of Shiraz University of Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

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