Net N-C charge imbalance may be important for signal sequence function in bacteria

The net charge distribution in a region around the signal sequence cleavage site has been calculated for samples of 41 prokaryotic and 165 eukaryotic exported proteins. The results show that prokaryotic proteins in particular have a markedly higher incidence of acidic than of basic residues in this region. The possibility that a “dipolar” structure with a positive net charge difference between the N and C-terminal regions is important for signal sequence function in bacteria is suggested, and invoked to rationalize a number of known export-defective signal sequence mutations.