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We investigate the interaction of various htt<jats:sup>ex1<\/jats:sup> constructs with the bacterial analog (GroEL) of the human chaperonin Hsp60. Using fluorescence spectroscopy and electron and atomic force microscopy, we show that GroEL inhibits fibril formation. The binding kinetics of htt<jats:sup>ex1<\/jats:sup> constructs with intact GroEL and a mini\u2010chaperone comprising the apical domain is characterized by relaxation\u2010based NMR measurements. The lifetimes of the complexes range from 100 to 400\u2005\u03bcs with equilibrium dissociation constants (<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>) of \u223c1\u20132\u2005mM. The binding interface is formed by the N\u2010terminal amphiphilic region of htt<jats:sup>ex1<\/jats:sup> (which adopts a partially helical conformation) and the H and I helices of the GroEL apical domain. Sequestration of monomeric htt<jats:sup>ex1<\/jats:sup> by GroEL likely increases the critical concentration required for fibrillization.<\/jats:p>","DOI":"10.1002\/cbic.202100055","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T22:26:38Z","timestamp":1614551198000},"page":"1985-1991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Probing the Interaction of Huntingtin Exon\u20101 Polypeptides with the Chaperonin Nanomachine GroEL"],"prefix":"10.1002","volume":"22","author":[{"given":"Marielle A.","family":"W\u00e4lti","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Physics National Institute of Diabetes and Digestive and Kidney Diseases  5 Memorial Drive Bethesda MD 20892-0520 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel A.","family":"Kotler","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Physics National Institute of Diabetes and Digestive and Kidney Diseases  5 Memorial Drive Bethesda MD 20892-0520 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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