{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:00:21Z","timestamp":1787065221641,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21973024"],"award-info":[{"award-number":["21973024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21773012"],"award-info":[{"award-number":["21773012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91753118"],"award-info":[{"award-number":["91753118"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["B2016201034"],"award-info":[{"award-number":["B2016201034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Hebei Province","award":["21973024"],"award-info":[{"award-number":["21973024"]}]},{"name":"Natural Science Foundation of Hebei Province","award":["21773012"],"award-info":[{"award-number":["21773012"]}]},{"name":"Natural Science Foundation of Hebei Province","award":["91753118"],"award-info":[{"award-number":["91753118"]}]},{"name":"Natural Science Foundation of Hebei Province","award":["B2016201034"],"award-info":[{"award-number":["B2016201034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Amyloid fibrillation of \u03b1-synuclein is implicated in the pathogenesis of Parkinson\u2019s disease and heavy metal ions such as Fe3+, Zn2+, and Cu2+ are known to be involved in the process. In this work, we explored the use of FTIR spectroscopy to look into the modulation effects of Fe3+, Zn2+, and Cu2+ on the amyloid fibrillation of \u03b1-synuclein. We performed a curve-fitting analysis on the FTIR amide I bands of these \u03b1-synuclein fibril systems, namely, the pristine fibril and the fibrils prepared in the presence of Fe3+, Zn2+, and Cu2+. We found that the \u03b1-synuclein fibrils under the influences of metal ions all possessed a parallel \u03b2-sheet structure, turn structure, and disordered structure, similar to that of pristine \u03b1-synuclein fibril. We also observed metal-induced increases in the proportions of the \u03b2-sheet secondary structure within the \u03b1-synuclein fibrils, with Fe3+ being the most effective inducer. We performed second derivative analysis of the side chain carboxylic groups of \u03b1-synuclein fibrils and found that the side chain microenvironment of the \u03b1-synuclein fibrils was more influenced by Fe3+ than Zn2+, and Cu2+. In addition, our atomic force microscopic study revealed that the morphologies of \u03b1-synuclein fibrils under the influence of Fe3+ was quite different from that of the Zn2+ and Cu2+ systems. Our FTIR results suggested that the modulation effects of Fe3+, Zn2+, and Cu2+ on \u03b1-synuclein fibrillation occurred at both secondary and quaternary structural levels. At last, we proposed a mechanistic hypothesis to interpret how metal ions could affect the morphology of \u03b1-synuclein amyloid fibril based on the conformational plasticity properties of intrinsically disordered proteins.<\/jats:p>","DOI":"10.3390\/molecules27238383","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T03:03:41Z","timestamp":1669863821000},"page":"8383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Modulation Effects of Fe3+, Zn2+, and Cu2+ Ions on the Amyloid Fibrillation of \u03b1-Synuclein: Insights from a FTIR Investigation"],"prefix":"10.3390","volume":"27","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4705-145X","authenticated-orcid":false,"given":"Gang","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/35081564","article-title":"Alpha-synuclein and neurodegenerative diseases","volume":"2","author":"Goedert","year":"2001","journal-title":"Nat. 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