Different modes of membrane interactions of the signal sequence of carp preproinsulin and of the insertion sequence of rabbit cytochrome b5.

The signal segment of the secretory protein carp preproinsulin is shown to be bound by a protein receptor present in the rough endoplasmic reticulum membrane. The receptor does not bind the insertion segment of the integral membrane protein cytochrome b5. On the other hand, the insertion sequence, in contrast to the signal sequence, is dissolved into the lipid bilayer of natural and artificial membranes. Hydrophobicity or length per se of the two types of peptides cannot be responsible for their different behaviour. We rather propose that the difference resides in their tertiary structure. Insertion peptides may form a compact structure with a diffuse hydrophobic surface, presumably by internal hydrogen bonding. Signal peptides would form hydrogen bonds with a membrane-bound receptor protein, presumably by producing a beta-sheet structure, but their extended structure in aqueous solution would not allow them to dissolve into lipid bilayers.