Letter abstract
Nature Cell Biology 8, 1155 - 1162 (2006)
Published online: 17 September 2006 | doi:10.1038/ncb1477
The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions
Stephen Tam1,2, Ron Geller2, Christoph Spiess2 & Judith Frydman2
Abstract
Misfolding and aggregation of proteins containing expanded polyglutamine repeats underlie Huntington's disease and other neurodegenerative disorders1. Here, we show that the hetero-oligomeric chaperonin TRiC (also known as CCT) physically interacts with polyglutamine-expanded variants of huntingtin (Htt) and effectively inhibits their aggregation. Depletion of TRiC enhances polyglutamine aggregation in yeast and mammalian cells. Conversely, overexpression of a single TRiC subunit, CCT1, is sufficient to remodel Htt-aggregate morphology in vivo and in vitro, and reduces Htt-induced toxicity in neuronal cells. Because TRiC acts during de novo protein biogenesis2, this chaperonin may have an early role preventing Htt access to pathogenic conformations. Based on the specificity of the Htt–CCT1 interaction, the CCT1 substrate-binding domain may provide a versatile scaffold for therapeutic inhibitors of neurodegenerative disease.
- Biophysics Graduate Program, Stanford University, Stanford, California 94305, USA.
- Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.
Correspondence to: Judith Frydman2 e-mail: jfrydman@stanford.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Research HighlightsNature Structural & Molecular Biology News and Views (01 Aug 2004)
Dangerous liaisons: polyglutamine meets HMGBNature Cell Biology News and Views (01 Apr 2007)
See all 4 matches for News And ViewsRESEARCH
Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation stateNature Cell Biology Letter (01 Oct 2006)
EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomersNature structural & molecular biology Article (01 Jun 2008)
See all 43 matches for Research
