Signal peptide subsegments are not always functionally interchangeable. M13 procoat hydrophobic core fails to transport alkaline phosphatase in Escherichia coli.

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Citation

Laforet GA, Kaiser ET, Kendall DA

Signal peptide subsegments are not always functionally interchangeable. M13 procoat hydrophobic core fails to transport alkaline phosphatase in Escherichia coli.

J Biol Chem. 1989 Aug 25;264(24):14478-85.

PubMed ID
2668291 [ View in PubMed
]
Abstract

Bacterial signal peptides display little amino acid sequence homology despite their shared role in mediating protein transport. This heterogeneity may exist to permit the establishment of signal peptide conformations that are appropriate for transport of particular proteins. In this paper we explore how signal peptides are composed of structural units that may interact with each other and with the mature protein to effect transport. Using a new application of cassette mutagenesis, we have replaced the hydrophobic core of the Escherichia coli alkaline phosphatase signal peptide with cores from the signals of maltose-binding protein, OmpA, and M13 major coat protein. The core regions from maltose-binding protein and OmpA effectively replaced the alkaline phosphatase core; the resultant hybrid signals performed as well as wild type in periplasmic transport and processing of alkaline phosphatase. However, the core region from M13 major coat protein generated a transport-incompetent hybrid signal peptide. Elimination of a proline-containing portion of the M13 major coat protein core did not improve transport effectiveness. However, restoration of the procoat cleavage region and the negatively charged amino terminus of the mature protein did ameliorate the transport defect. These results suggest that at least in the case of these procoat-derived signal peptide mutants, there is a requirement for complementarity among the hydrophobic core, cleavage region, and part of the mature protein in order for efficient protein transport to occur.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Alkaline phosphataseP00634Details