Life and death of a signal peptide

Signal peptides target proteins for secretion in both prokaryotic and eukaryotic cells. A deceptively simple-looking amino-terminal extension on the newly synthesized polypeptide chain, the signal peptide takes part in an array of protein-protein and protein-lipid interactions. The result is initiation of protein translocation through a proteinaceous channel — the translocon — in the bacterial inner membrane, or in the endoplasmic reticulum (ER) of eukaryotic cells. After fulfilling its mission, the signal peptide receives its coup de grâce from the signal peptidase, a membrane-bound enzyme that liberates the mature protein from this now useless appendage.

Thanks to the work of Paetzel et al. 1, who report the crystal structure of a bacterial signal peptidase on page 186 of this issue, we now have a glimpse of how this unusual enzyme can cleave the signal peptide so precisely as it emerges from the relative safety of the membrane. Not only do we see a new protease fold and a strikingly hydrophobic surface patch that positions the active site relative to the lipid bilayer, but the structure of the bacterial enzyme can also be used as a template to model other signal peptidases, and will be of great interest for designing new antibiotics.

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Figure 1: The signal peptidase of Escherichia coli, the structure of which has been solved by Paetzel et al.1.

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Authors and Affiliations

1. The Department of Biochemistry, Arrhenius Laboratories, Stockholm University, S-106 91, Stockholm, Sweden

   Gunnar von Heijne

Authors

1. Gunnar von Heijne

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von Heijne, G. Life and death of a signal peptide. Nature 396, 111–113 (1998). https://doi.org/10.1038/24036

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• Issue date: 12 November 1998

• DOI: https://doi.org/10.1038/24036