A Lys27‐to‐Glu27 mutation in the human insulin‐like growth factor‐1 prevents disulfide linked dimerization and allows secretion of BiP when expressed in yeast

FEBS Letters

Priestle, John P.¹  Chaudhuri, Bhabatosh¹  Helliwell, Stephen B.¹ 

[1] Department of Biotechnology, Ciba-Geigy Ltd., CH-4002 Basel, Switzerland

关键词: Insulin-like growth factor 1;    Dimerization;    Intermolecular disulfide bond;    Folding/malfolding in vivo;    BiP secretion;    Saccharomyces cerevisiae;    BiP;    heavy chain binding protein;    BPTI;    bovine oancreatic trypsin inhibitor;    DTT;    dithiothreitol;    ER;    endoplasmic reticulum;    hIGF1;    human insulin-like growth factor-1;    HPLC;    high performance liquid chromatography;    PMSF;    phenyl-methane-sulfonyl-fluoride;    RNase A;    ribonucleaseA;    TCA;    trichloroacetic acid;    wt;    wild type;   

DOI  :  10.1016/0014-5793(91)81432-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recombinant human insulin-like growth factor-1 (IGF1) secreted from yeast contains only 10–15% of the active monomer. A majority of the IGF1-like molecules are disulfide bonded dimers. These dimers are not formed in an IGF1 mutant where Lys²⁷ has been replaced by glutamic acid. However, increased levels of secreted BiP (the yeast KAR2 gene product) are seen in cells expressing the mutant. These results imply that by preventing ionic interactions between two IGF1 molecules, intermolecularm disulfide bonds do not form in yeast, and that in the mutant there is a structural change which induces BiP, allowing its secretion.

【 授权许可】

Unknown