The functional efficiency of a mammalian signal peptide is directly related to its hydrophobicity

Phillip Bird, Mary Jane Gething, Joe Sambrook

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We have previously shown that the signal sequence of the Saccharomyces cerevisiae vacuolar protein carboxypeptidase Y (CPY) does not function in mammalian cells unless a glycine residue in the central core is replaced by leucine. Additional mutants were constructed to investigate the features of this hydrophobic core (h) region that are important for signal sequence function in mammalian cells. We find that the degree of hydrophobicity of the h region of any particular mutant signal is directly related to the efficiency with which it directs the translocation of CPY. A minimal h region in a functional signal appears to consist of five hydrophobic residues interrupted by 1 glycine. Analysis of potential secondary structures suggests that a functional mutant signal is more likely than the nonfunctional CPY signal to adopt either a β strand or an α-helical conformation.

Original languageEnglish
Pages (from-to)8420-8425
Number of pages6
JournalJournal of Biological Chemistry
Issue number15
Publication statusPublished - 25 May 1990
Externally publishedYes

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