{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:41:03Z","timestamp":1789512063193,"version":"build-2803163510"},"reference-count":33,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009888","name":"Regione Toscana","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Recovery and Resilience Plan"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,22]]},"abstract":"<jats:p>Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the \u03b2-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AAt) for the amyloid \u03b2 (A\u03b2) peptide, \u03b1-synuclein (\u03b1S), and the 4R isoforms of tau, associated with Alzheimer\u2019s disease, Parkinson\u2019s disease, and various tauopathies, respectively. This approach enabled a statistical analysis of sequences forming \u03b2-sheet regions in amyloid polymorphs. We computed for any given sequence residue n the fraction of PDB\/AAt structures in which that residue adopts a \u03b2-sheet conformation (F\u03b2(n)) to generate an experimental, structure-based profile of F\u03b2(n) vs n, which represents the \u03b2-conformational preference of any residue in the amyloid state. The peaks in the respective F\u03b2(n) profiles of the three proteins, corresponding to sequence regions adopting more frequently the \u03b2-sheet structural core in the various fibrillar structures, align very well with the peaks identified with five predictive algorithms (ZYGGREGATOR, TANGO, PASTA, AGGRESCAN, and WALTZ). These results indicate that, despite amyloid polymorphism, sequence regions most often forming the structural core of amyloid have high hydrophobicity, high intrinsic \u03b2-sheet propensity and low electrostatic charge across the sequence, as rationalised and predicted by the algorithms.<\/jats:p>","DOI":"10.1042\/bcj20240602","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T20:51:32Z","timestamp":1734555092000},"page":"87-101","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins"],"prefix":"10.1042","volume":"482","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6197-9740","authenticated-orcid":false,"given":"Silvia","family":"Errico","sequence":"first","affiliation":[{"name":"1Department of Experimental and Clinical Biomedical Sciences \"Mario Serio\", Section of Biochemistry, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-7811","authenticated-orcid":false,"given":"Giulia","family":"Fani","sequence":"additional","affiliation":[{"name":"1Department of Experimental and Clinical Biomedical Sciences \"Mario Serio\", Section of Biochemistry, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9652-6351","authenticated-orcid":false,"given":"Salvador","family":"Ventura","sequence":"additional","affiliation":[{"name":"2Institut de Biotecnologia i de Biomedicina (IBB) and Departament de Bioqu\u00edmica i Biologia Molecular, Universitat Aut\u00f2noma de Barcelona, 08193 Bellaterra, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-0168","authenticated-orcid":false,"given":"Joost","family":"Schymkowitz","sequence":"additional","affiliation":[{"name":"3Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"4Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"},{"name":"5Switch Laboratory, VIB Center for AI & Computational Biology, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Rousseau","sequence":"additional","affiliation":[{"name":"3Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"4Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"},{"name":"5Switch Laboratory, VIB Center for AI & Computational Biology, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1596-9477","authenticated-orcid":false,"given":"Antonio","family":"Trovato","sequence":"additional","affiliation":[{"name":"6Department of Physics and Astronomy \"G. Galilei\", University of Padova, 35131 Padova, Italy"},{"name":"7National Institute of Nuclear Physics (INFN), Padova Section, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-1610","authenticated-orcid":false,"given":"Michele","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"8Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, CB21EW Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0643-6249","authenticated-orcid":false,"given":"Francesco","family":"Bemporad","sequence":"additional","affiliation":[{"name":"1Department of Experimental and Clinical Biomedical Sciences \"Mario Serio\", Section of Biochemistry, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1330-1289","authenticated-orcid":false,"given":"Fabrizio","family":"Chiti","sequence":"additional","affiliation":[{"name":"1Department of Experimental and Clinical Biomedical Sciences \"Mario Serio\", Section of Biochemistry, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"2025020309304832000_BCJ-2024-0602C1","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1073\/pnas.75.9.4499","article-title":"Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy","volume":"75","author":"Costa","year":"1978","journal-title":"Proc. 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