Signal peptides: exquisitely designed transport promoters

Mol Microbiol. 1994 Sep;13(5):765-73. doi: 10.1111/j.1365-2958.1994.tb00469.x.


Prokaryotic proteins destined for transport out of the cytoplasm typically contain an N-terminal extension sequence, called the signal peptide, which is required for export. It is evident that many secretory proteins utilize a common export system, yet the signal sequences themselves display very little primary sequence homology. In attempting to understand how different signal peptides are able to promote protein secretion through the same pathway, the physical features of natural signal sequences have been extensively examined for similarities that might play a part in function. Experimental data have confirmed statistical analyses which highlighted dominant features of natural signal sequences in Escherichia coli: a net positive charge in the N-terminus increases efficiency of transport; the core region must maintain a threshold level of hydrophobicity within a range of length limitations; the central portion adopts an alpha-helical conformation in hydrophobic environments; and the signal cleavage region is ideally six residues long, with small side-chain amino acids in the -1 and -3 positions. This review focuses on the parallels between signal peptide physical features and their functions, which emerge when the results of a variety of experimental approaches are combined. The requirement for each property may be ascribed to a potential interaction that is critical for efficient protein export. The summation of the key physical features produces signal peptides with the flexibility to function in multiple roles in order to expedite secretion. In this way, nature has indeed evolved exquisitely tuned signal sequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acids / chemistry
  • Bacteria / genetics
  • Bacterial Physiological Phenomena*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Biological Transport / physiology*
  • Cell Membrane / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / physiology
  • Membrane Lipids / metabolism
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein Conformation
  • Protein Sorting Signals / chemistry
  • Protein Sorting Signals / genetics
  • Protein Sorting Signals / physiology*


  • Amino Acids
  • Bacterial Proteins
  • Membrane Lipids
  • Protein Sorting Signals