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Huntingtin's spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function
KTH, School of Technology and Health (STH), Basic Science and Biomedicine, Structural Biotechnology. Korea Adv Inst Sci & Technol, KAIST Inst BioCentury, Korea.
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2016 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 5, e11184Article in journal (Refereed) PublishedText
Abstract [en]

The polyglutamine expansion in huntingtin protein causes Huntington's disease. Here, we investigated structural and biochemical properties of huntingtin and the effect of the polyglutamine expansion using various biophysical experiments including circular dichroism, single particle electron microscopy and cross-linking mass spectrometry. Huntingtin is likely composed of five distinct domains and adopts a spherical alpha-helical solenoid where the amino-terminal and carboxyl-terminal regions fold to contain a circumscribed central cavity. Interestingly, we showed that the polyglutamine expansion increases alpha-helical properties of huntingtin and affects the intramolecular interactions among the domains. Our work delineates the structural characteristics of full-length huntingtin, which are affected by the polyglutamine expansion, and provides an elegant solution to the apparent conundrum of how the extreme amino-terminal polyglutamine tract confers a novel property on huntingtin, causing the disease.

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Structural Biology
URN: urn:nbn:se:kth:diva-185632DOI: 10.7554/eLife.11184ISI: 000373331100001ScopusID: 2-s2.0-84964285135OAI: diva2:924815

QC 20160429

Available from: 2016-04-29 Created: 2016-04-25 Last updated: 2016-04-29Bibliographically approved

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