A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: Evidence for a compact beta-sheet structure

Michelle A. Poirier, Haibing Jiang, Christopher A. Ross

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)765-774
Number of pages10
JournalHuman molecular genetics
Volume14
Issue number6
DOIs
StatePublished - Mar 15 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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