Huntingtin’s spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function

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Huntingtin’s spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function

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Title: Huntingtin’s spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function
Author: Vijayvargia, Ravi; Epand, Raquel; Leitner, Alexander; Jung, Tae-Yang; Shin, Baehyun; Jung, Roy; Lloret, Alejandro; Singh Atwal, Randy; Lee, Hyeongseok; Lee, Jong-Min; Aebersold, Ruedi; Hebert, Hans; Song, Ji-Joon; Seong, Ihn Sik

Note: Order does not necessarily reflect citation order of authors.

Citation: Vijayvargia, R., R. Epand, A. Leitner, T. Jung, B. Shin, R. Jung, A. Lloret, et al. 2016. “Huntingtin’s spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function.” eLife 5 (1): e11184. doi:10.7554/eLife.11184. http://dx.doi.org/10.7554/eLife.11184.
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Abstract: 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 α-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 α-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. DOI: http://dx.doi.org/10.7554/eLife.11184.001
Published Version: doi:10.7554/eLife.11184
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846397/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860048
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