Prediction of the site of signal peptidase cleavage in normal and variant human preproalbumin.

We describe the use of a template for the recognition site of signal peptidase to give score predictions for cleavage at normal and aberrant sites in human and chicken preproalbumin. As expected, the highest score obtained for human preproalbumin was at the normal cleavage site between -7 Ser and -6 Arg. The mutation in preproalbumin Kaikoura (-2 Arg----Cys) introduced an aberrant cleavage site in the propeptide between the new -2 Cys and -1 Arg. Although the new site had a lower template score (6.88) than the normal site (9.99), it is cleaved in vivo about five times faster. The presence of minor proportions of des-Asp and des-Asp-Ala-albumin in normal human plasma was not found to correlate with possible aberrant signal peptidase cleavage. These truncated albumin species, therefore, appear to be generated through cleavage of mature albumin in circulation. Chicken preproalbumin had only one probably signal peptidase cleavage site, the one utilised in vivo. Template scores should be regarded as qualitative predictions rather than definitive quantitative indicators.