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Research Article

Polyglutamine Induced Misfolding of Huntingtin Exon1 is Modulated by the Flanking Sequences

  • Vinal V. Lakhani,

    Affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America

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  • Feng Ding,

    Affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America

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  • Nikolay V. Dokholyan mail

    dokh@med.unc.edu

    Affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America

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  • Published: April 29, 2010
  • DOI: 10.1371/journal.pcbi.1000772

Reader Comments (1)

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N17 resisting Aggregation

Posted by RayTruant on 06 May 2010 at 14:55 GMT

The authors make reference to our past work by Atwal, et al., Hum Mol Genet. 2007 Nov 1;16(21):2600-15, stating that we imply that huntingtin N17 resists aggregation.

Our conclusions from that study were in fact the opposite. We showed that a single point mutation within N17, a proline substitution at position eight, disrupted all structure of N17 and completely prevented any aggregation of 1-171, even at Q250 lengths and massive over-expression. However, wild-type N17 was required for the presence of any visible aggregates.

No competing interests declared.

RE: N17 resisting Aggregation

dokh replied to RayTruant on 07 May 2010 at 03:51 GMT

During preparation of our manuscript, we accidentally equated toxicity with aggregation and thus misinterpreted the latter conclusion to read that the native structure of Nt17 prevents aggregation. There is no proof that aggregation causes toxicity; instead, there is mounting evidence for a negative correlation between aggregation and cell death. Our purpose was to illustrate the current debate on whether the Nt17 region promotes or inhibits aggregation of XN1. In error, we inappropriately place the above mentioned article on the side of inhibiting aggregation. Correct citations would strengthen the evidence for Nt17 promoting aggregation but does not conclude the debate. This mistake does not alter the main conclusions or discussion of our manuscript.

No competing interests declared.