Role of the hydrophobic region of signal sequences in the targeting of proteins to membranes and translocation across the hydrophobic membrane barrier

Proteins destined for regions other than the cytoplasm in cells have to cross at least one membrane barrier before reaching their proper destination. Almost all such proteins are initially biosynthesized as precursors with signal sequences at the amino terminus. Signal sequences are essential and also sufficient for proteins to be targeted to membranes and also for translocation across membranes. One striking feature that is clearly evident amongst signal sequences of secretory proteins is a positively charged amino terminus followed by a region comprising 10-12 very hydrophobic amino acids. The structural and physico-chemical properties of signal sequences have been analysed. On the basis of the analyses it is proposed that the structural feature of a positively charged amino terminal region followed by a hydrophobic stretch of amino acids, rather than a conformational one, is recognised by components of the cells export machinery. It is also postulated that signal sequences insert in the lipid bilayer of the translocation competent membrane after targeting. The presence of the signal sequence results in the formation of local 'defects' in the bilayer which have a role in translocation of proteins across membranes. © 1987 Indian Academy of Sciences.