The functional efficiency of a mammalian signal peptide is directly related to its hydrophobicity.
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 beta strand or an alpha-helical conformation.
Bird
P
P
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Gething
M J
MJ
Sambrook
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002268:Carboxypeptidases / Q000235:genetics*; D043402:Cathepsin A; D002460:Cell Line; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship; D014162:Transfection; D014617:Vacuoles / Q000201:enzymology
D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins; D002268:Carboxypeptidases; D043402:Cathepsin A; C499283:PRC1 protein, S cerevisiae; C022633:serine carboxypeptidase