Functional and nonfunctional LamB signal sequences can be distinguished by their biophysical properties.

The role of the signal sequence in the secretion of proteins remain unclear despite extensive research. We have examined properties of synthetic peptides corresponding to a family of signal sequences derived from the lamB gene of Escherichia coli, including five examples of known phenotype that contain mutations in the signal sequence. By circular dichroism spectroscopy, the wild type and export-component mutant signal peptides show a high alpha-helix content in membrane mimetic environments (sodium dodecyl sulfate micelles and phospholipid vesicles). Tendency to adopt helical conformations is clearly not sufficient to define a functional signal sequence, however, as some nonfunctional mutant signal peptides also contain a relatively high proportion of alpha-helix. The affinity of these peptides for phospholipid monolayers as assessed by surface tensiometry reveals further distinguishing properties. Export-competent peptides show an increased affinity for and greater perturbation of phospholipid monolayers and bilayers than to export-defective peptides. These results suggest a lipid binding role for the signal sequence during protein export in addition to its recognition by proteins of the export pathway.