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To disentangle the mechanistic underpinnings of these dynamical properties, we mutated a conserved IXI-motif located within the N-terminal (NT) domain of human \u03b1B-crystallin. This resulted in a profound structural transformation, from highly polydispersed caged-like native assemblies into a comparatively well-ordered helical fibril state amenable to high-resolution cryo-EM analysis. The reversible nature of the induced fibrils facilitated interrogation of functional effects due to perturbation of the NT-IXI motif in both the native-like oligomer and fibril states. Together, our investigations unveiled several features thought to be key mechanistic attributes to sHSPs and point to a critical significance of the NT-IXI motif in \u03b1B-crystallin assembly, dynamics and chaperone activity.<\/jats:p>","DOI":"10.1101\/2024.03.22.586355","type":"posted-content","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T14:55:45Z","timestamp":1711551345000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic fibrillar assembly of \u03b1B-crystallin induced by perturbation of the conserved NT-IXI motif resolved by cryo-EM"],"prefix":"10.64898","author":[{"given":"Russell","family":"McFarland","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5276-7690","authenticated-orcid":false,"given":"Steve","family":"Reichow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024032912050605000_2024.03.22.586355v1.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10449"},{"key":"2024032912050605000_2024.03.22.586355v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(18)53882-5"},{"key":"2024032912050605000_2024.03.22.586355v1.3","doi-asserted-by":"crossref","first-page":"167157","DOI":"10.1016\/j.jmb.2021.167157","article-title":"The Diverse Functions of Small Heat Shock Proteins in the Proteostasis Network","volume":"434","year":"2022","journal-title":"J Mol Biol"},{"key":"2024032912050605000_2024.03.22.586355v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.01.004"},{"key":"2024032912050605000_2024.03.22.586355v1.5","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(2003)8<53:THGECS>2.0.CO;2"},{"key":"2024032912050605000_2024.03.22.586355v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0141-8130(98)00013-0"},{"key":"2024032912050605000_2024.03.22.586355v1.7","doi-asserted-by":"publisher","DOI":"10.1177\/38.1.2294148"},{"key":"2024032912050605000_2024.03.22.586355v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2014.02.006"},{"key":"2024032912050605000_2024.03.22.586355v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2014.12.019"},{"key":"2024032912050605000_2024.03.22.586355v1.10","doi-asserted-by":"crossref","unstructured":"Sarparanta, J. , Jonson, P.H. , Kawan, S. & Udd, B . 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