Toxicity of expanded polyglutamine‐domain proteins in Escherichia coli

FEBS Letters

Vance, Jeffery M.²  Burke, James R.²  Strittmatter, Warren J.²  Tsuji, Shoji¹  Rose, Allen D.²  Onodera, Osamu² 

[1] Department of Neurology, Niigata University, Niigata, Japan;Department of Medicine (Neurology), Box 2900, Duke University Medical Center, Durham, NC 27710, USA

关键词: Polyglutamine;    Trinucleotide repeat;    CAG repeat;    Pathogenesis;    Huntington's disease;    DRPLA;    (E. coli);    DRPLA;    dentatorubral pallidoluysian atrophy;    SCA1;    spinocerebellar ataxia I;    SBMA;    spinobulbar muscular atrophy;    MJD;    Machado-Joseph disease;    IPTG;    isopropylthio-β-d-galactoside;    Q1081;    number of uninterrupted glutamines in clone;    GST;    glutathione-S-transferase;    A61-SR;    clone containing 61 alanines with a carboxyl terminal serine and arginine;    Q62-SR;    clone containing 62 glutamines with a carboxyl terminal serine and arginine;   

DOI  :  10.1016/S0014-5793(96)01301-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Five neurodegenerative diseases are caused by proteins with expanded polyglutamine domains. Toxicity of these proteins has been previously identified only in mammals, and no simple model systems are available. In this paper, we demonstrate in E. coli that long polyglutamine domains (59–81 residues) as GST-fusion proteins inhibit growth while smaller glutamine (10–35 residues) or polyalanine (61 residues) domains have no effect. Analogously in humans, polyglutamine repeats less than 35–40 glutamines produce a normal phenotype, while expansion greater than 40 glutamines is always associated with disease. Expression of polyglutamine proteins in E. coli may help identify the molecular mechanism of pathogenesis of CAG trinucleotide repeat diseases and be a useful screen to identify potential therapeutic compounds.

【 授权许可】

Unknown