Toxicity of expanded polyglutamine-domain proteins in Escherichia coli.
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 compound.
Onodera
O
O
Department of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA.
Roses
A D
AD
Tsuji
S
S
Vance
J M
JM
Strittmatter
W J
WJ
Burke
J R
JR
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry / Q000633:toxicity*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000633:toxicity
D010455:Peptides; D011506:Proteins; D011993:Recombinant Fusion Proteins; C097188:polyglutamine; D005982:Glutathione Transferase