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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 \u03b1-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 \u03b1-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.<\/jats:p>","DOI":"10.7554\/elife.11184","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T08:30:17Z","timestamp":1458635417000},"source":"Crossref","is-referenced-by-count":61,"title":["Huntingtin\u2019s spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function"],"prefix":"10.7554","volume":"5","author":[{"given":"Ravi","family":"Vijayvargia","sequence":"first","affiliation":[{"name":"Center for Human Genetic Research, Massachusetts General Hospital, Boston, United States"},{"name":"Department of Neurology, Harvard Medical School, Boston, United 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