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Updated: Aug 19, 2026

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
Published on: June 27, 2018
A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact
Michelle A Poirier1, Haibing Jiang, Christopher A Ross
1Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. mpoirie1@jhmi.edu
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.
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