Atomic force microscopy analysis of the Huntington protein nanofibril formation

Paul R. Dahlgren, Mikhail A. Karymov, John Bankston, Tina Holden, Peter Thumfort, Vernon M. Ingram, Yuri L. Lyubchenko

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background: Huntington's disease is an autosomal dominant progressive neurodegenerative disease associated with dramatic expansion of a polyglutamine sequence in exon 1 of the huntingtin protein htt that leads to cytoplasmic, and even nuclear aggregation of fibrils. Methods: We have studied the in vitro fibril formation of mutant exon 1, and the shorter wild-type exon 1, with use of atomic force microscopy (AFM). Results: Large aggregates are formed spontaneously after cleavage of the glutathione-S-transferase fusion protein of the mutant exon 1 protein. The AFM data showed that, unlike fibrils assembled by such proteins as amyloid β-peptide and α-synuclein, htt forms fibrils with extensive branched morphologic features. Branching can be observed even at earlier stages of the htt self-assembly, but the effect is much more pronounced at late stages of aggregation. We also found that fusing of htt with green fluorescent protein does not change the branched-type morphologic features of the aggregates. Conclusions: On the basis of the results obtained, we propose a model for htt fibrillization that explains branched morphologic features of the aggregates.

Original languageEnglish (US)
Pages (from-to)52-57
Number of pages6
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Issue number1
StatePublished - Mar 2005
Externally publishedYes


  • Atomic force microscopy
  • Huntington's disease
  • Nanofibrils

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


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