Question

Describe the key properties of a signal sequence (or leader sequence or leader peptide). Explain the roles of these properties in guiding proteins across the cytoplasmic membrane. .

Answer 1

A signal peptide is a short sequence of amino acids, about 16-30, that are a part of some proteins which are newly synthesized and are involved in the secretory pathway. The signal peptide is located at the N terminus of the protein. The proteins which present with signal peptide reside either inside certain organelles involved in secretory pathway like endoplasmic reticulum, Golgi apparatus, secreted by the cell, or get inserted into the cell membranes. Some examples of these proteins are Type I membrane-bound proteins. Type II and multispanning membrane-bound proteins (involved in the secretory pathway) also have peptides biochemically similar to signal peptides but are not cleaved so they are more commonly referred to as target peptides. The signal peptides have a tripartite structure with an n-region that is positively charged (it ensures proper topology of the protein with a positive inside rule), h-region that is hydrophobic (forms the core region and forms a single alpha helix), and a c-region that serves as a cleavage site (can be cleaved by a signal peptidase).

The above-listed features hint in one direction i.e., the main function of signal peptides is in translocation of proteins to the cell membrane. Signal peptides in prokaryotes direct the newly synthesized proteins to the SecYEG protein-conducting channel located in the plasma membrane. A similar homologous system exists in eukaryotes. In eukaryotes, the signal peptide directs the newly synthesized protein to a protein conducting channel, Sec61 that is present in the endoplasmic reticulum. Translocon is the name given to these conducting channels since they allow translocation of proteins. The cleavage occurs during or after the translocation to produce a mature protein and free signal peptide. It is generally done by signal peptidase.  

There is also a process of co-translocation that is activated when the signal peptide emerges from the ribosome and is recognized by signal-recognition peptide (SRP). Any further translation is arrested and the complex is transferred to the SRP receptor present on surface of cell membrane in prokaryotes and ER in eukaryotes. After this, the signal peptide gets inside translocon.  

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