title: Optimization of the signal-sequence cleavage site for secretion from Bacillus subtilis of a 34-amino acid fragment of human parathyroid hormone.
abstract: We have effected the secretion from Bacillus subtilis of a 34-amino acid (aa) fragment of human parathyroid hormone (PTH,1-34), using a Bacillus amyloliquefaciens neutral protease signal sequence. The secretion efficiency depended on the aa sequence near the signal-sequence cleavage site. We constructed a series of gene fusions encoding different pairs of aa between the signal sequence and PTH,1-34. There was a correlation between those polypeptides which were efficiently secreted and the potential for a beta-turn in the region just beyond the signal-sequence cleavage site. Based on this correlation, we constructed a gene fusion which specified Gly rather than Ala at the C terminus of the signal sequence, thus creating a beta-turn potential at the end of the signal sequence. The change provided a slight increase in secretion efficiency.
authors.affiliation: Corporate Research Division, Procter and Gamble Company, Cincinnati, OH 45239-8707.
authors.forename: C W
authors.initials: CW
authors.lastname: Saunders
authors.forename: J A
authors.initials: JA
authors.lastname: Pedroni
authors.forename: P M
authors.initials: PM
authors.lastname: Monahan
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D004247:DNA; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010281:Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D010281:Parathyroid Hormone; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D004247:DNA