caa a22 4500 528785478 20190908091347.0 cr unu---uuuuu 180924s2016 xx s 000 0 eng 10.3929/ethz-b-000114979 doi 10.7554/eLife.11184 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/114979 Huntingtin's spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function [Elektronische Daten] [Ravi Vijayvargia, Raquel F. Epand, Alexander Leitner, Tae-Yang Jung, Baehyun Shin, Roy Jung, Alejandro Lloret, Randy S. Atwal, Hyeongseok Lee, Jong-Min Lee, Ruedi Aebersold, Hans Hebert, Ji-Joon Song, Ihn Sik Seong] Open access ethresearch 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. Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 ethresearch Vijayvargia Ravi joint author Epand Raquel F. joint author Leitner Alexander joint author Jung Tae-Yang joint author Shin Baehyun joint author Jung Roy joint author Lloret Alejandro joint author Atwal Randy S. joint author Lee Hyeongseok joint author Lee Jong-Min joint author Aebersold Ruedi joint author Hebert Hans joint author Song Ji-Joon joint author Seong Ihn Sik joint author eLife Cambridge : eLife Sciences Publications 5, p. e11184 2050-084X http://hdl.handle.net/20.500.11850/114979 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/114979 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Vijayvargia Ravi joint author ETHRESEARCH 700 1- Epand Raquel F. joint author ETHRESEARCH 700 1- Leitner Alexander joint author ETHRESEARCH 700 1- Jung Tae-Yang joint author ETHRESEARCH 700 1- Shin Baehyun joint author ETHRESEARCH 700 1- Jung Roy joint author ETHRESEARCH 700 1- Lloret Alejandro joint author ETHRESEARCH 700 1- Atwal Randy S. joint author ETHRESEARCH 700 1- Lee Hyeongseok joint author ETHRESEARCH 700 1- Lee Jong-Min joint author ETHRESEARCH 700 1- Aebersold Ruedi joint author ETHRESEARCH 700 1- Hebert Hans joint author ETHRESEARCH 700 1- Song Ji-Joon joint author ETHRESEARCH 700 1- Seong Ihn Sik joint author ETHRESEARCH 773 0- eLife Cambridge : eLife Sciences Publications 5, p. e11184 2050-084X BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access