Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell.
We investigated the effect of protein disulfide isomerase (PDI) on in vivo protein folding of human lysozyme (h-LZM) in a specially constructed yeast coexpression system. Coexpression with PDI increased the amounts of intracellular h-LZM with the native conformation, leading to an increase in h-LZM secretion. The results indicated that PDI is a real catalyst of protein folding in the cell. The secretion of h-LZM increased even when both active sites of PDI were disrupted, suggesting that the effect of PDI resulted from a function other than the formation of disulfide bonds. This is the first finding that PDI without isomerase activity accelerates protein folding in vivo.
Protein Engineering Research Institute, Osaka, Japan.
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Hayano
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Hirose
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Kikuchi
D001483:Base Sequence; D003001:Cloning, Molecular; D005784:Gene Amplification; D005822:Genetic Vectors; D006801:Humans; D007535:Isomerases / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009113:Muramidase / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
D018832:Molecular Chaperones; D011994:Recombinant Proteins; D009113:Muramidase; D007535:Isomerases; D019704:Protein Disulfide-Isomerases