Signal sequence function in the mammalian endoplasmic reticulum: A biological perspective

The discovery of the signal peptide, an amino-terminal protein sequence that specifies targeting of newly synthesized polypeptides to the endoplasmic reticulum (ER), stands as one of the most significant in cell biology. The signal peptide performs a targeting function in the cell and serves as a paradigm for the processes by which proteins are targeted to other organelles of the eukaryotic cell, such as the nucleus, the mitochondria, and the peroxisome. Central to signal sequence function is its composite secondary structure, a conserved tripartite motif consisting of a positively charged amino terminus, a central hydrophobic core, and a carboxy-terminal polar domain. Of the three domains, it is the central hydrophobic core, a continuous stretch of 7-15 hydrophobic amino acids, that is functionally dominant. By virtue of its mean hydrophobicity, the central hydrophobic domain disposes the signal sequence to direct interactions with the lipid bilayer. Nonetheless, the predominant view in the cell biology community is that signal sequences function through direct protein-protein interactions to specify both targeting to the ER and regulation of the protein translocation machinery. This review focuses on signal sequence function, with critical emphasis on discerning lipid-dependent versus protein-dependent interactions with and within the ER membrane. © 2002.

Duke Scholars

Author Christopher Vincent Nicchitta Cell Biology