Abstract
Huntington's disease (HD) arises from an expanded polyglutamine (polyQ) in the N-terminus of the huntingtin (htt) protein. Neuronal degeneration and inclusions containing N-terminal fragments of mutant htt are present in the cortex and striatum of HD brain. Recently, a model of polyQ aggregate structure has been proposed on the basis of studies with synthetic polyQ peptides and includes an alternating beta-strand/beta-turn structure with seven glutamine residues per beta-strand. We tested this model in the context of the htt exon-1 N-terminal fragment in both mammalian cell culture and cultured primary cortical neurons. We found our data support this model in the htt protein and provide a better understanding of the structural basis of polyQ aggregation in toxicity in HD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 765-774 |
| Number of pages | 10 |
| Journal | Human Molecular Genetics |
| Volume | 14 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2005 |
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ASJC Scopus subject areas
- Genetics
Cite this
A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity : Evidence for a compact beta-sheet structure. / Poirier, Michelle A.; Jiang, Haibing; Ross, Christopher A.
In: Human Molecular Genetics, Vol. 14, No. 6, 15.03.2005, p. 765-774.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity
T2 - Evidence for a compact beta-sheet structure
AU - Poirier, Michelle A.
AU - Jiang, Haibing
AU - Ross, Christopher A
PY - 2005/3/15
Y1 - 2005/3/15
N2 - Huntington's disease (HD) arises from an expanded polyglutamine (polyQ) in the N-terminus of the huntingtin (htt) protein. Neuronal degeneration and inclusions containing N-terminal fragments of mutant htt are present in the cortex and striatum of HD brain. Recently, a model of polyQ aggregate structure has been proposed on the basis of studies with synthetic polyQ peptides and includes an alternating beta-strand/beta-turn structure with seven glutamine residues per beta-strand. We tested this model in the context of the htt exon-1 N-terminal fragment in both mammalian cell culture and cultured primary cortical neurons. We found our data support this model in the htt protein and provide a better understanding of the structural basis of polyQ aggregation in toxicity in HD.
AB - Huntington's disease (HD) arises from an expanded polyglutamine (polyQ) in the N-terminus of the huntingtin (htt) protein. Neuronal degeneration and inclusions containing N-terminal fragments of mutant htt are present in the cortex and striatum of HD brain. Recently, a model of polyQ aggregate structure has been proposed on the basis of studies with synthetic polyQ peptides and includes an alternating beta-strand/beta-turn structure with seven glutamine residues per beta-strand. We tested this model in the context of the htt exon-1 N-terminal fragment in both mammalian cell culture and cultured primary cortical neurons. We found our data support this model in the htt protein and provide a better understanding of the structural basis of polyQ aggregation in toxicity in HD.
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UR - http://www.scopus.com/inward/citedby.url?scp=15544372340&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddi071
DO - 10.1093/hmg/ddi071
M3 - Article
C2 - 15689354
AN - SCOPUS:15544372340
VL - 14
SP - 765
EP - 774
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 6
ER -