{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:53:15Z","timestamp":1781106795927,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-30007"],"award-info":[{"award-number":["19-74-30007"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The coordination of zinc ions by histidine residues of amyloid-beta peptide (A\u03b2) plays a critical role in the zinc-induced A\u03b2 aggregation implicated in Alzheimer\u2019s disease (AD) pathogenesis. The histidine to arginine substitution at position 6 of the A\u03b2 sequence (H6R, English mutation) leads to an early onset of AD. Herein, we studied the effects of zinc ions on the aggregation of the A\u03b242 peptide and its isoform carrying the H6R mutation (H6R-A\u03b242) by circular dichroism spectroscopy, dynamic light scattering, turbidimetric and sedimentation methods, and bis-ANS and thioflavin T fluorescence assays. Zinc ions triggered the occurrence of amorphous aggregates for both A\u03b242 and H6R-A\u03b242 peptides but with distinct optical properties. The structural difference of the formed A\u03b242 and H6R-A\u03b242 zinc-induced amorphous aggregates was also supported by the results of the bis-ANS assay. Moreover, while the A\u03b242 peptide demonstrated an increase in the random coil and \u03b2-sheet content upon complexing with zinc ions, the H6R-A\u03b242 peptide showed no appreciable structural changes under the same conditions. These observations were ascribed to the impact of H6R mutation on a mode of zinc\/peptide binding. The presented findings further advance the understanding of the pathological role of the H6R mutation and the role of H6 residue in the zinc-induced A\u03b2 aggregation.<\/jats:p>","DOI":"10.3390\/biom10060961","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:36:54Z","timestamp":1593081414000},"page":"961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The English (H6R) Mutation of the Alzheimer\u2019s Disease Amyloid-\u03b2 Peptide Modulates Its Zinc-Induced Aggregation"],"prefix":"10.3390","volume":"10","author":[{"given":"Sergey P.","family":"Radko","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Institute of Biomedical Chemistry, 119121 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana A.","family":"Khmeleva","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, 119121 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry N.","family":"Kaluzhny","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga I.","family":"Kechko","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana Y.","family":"Kiseleva","sequence":"additional","affiliation":[{"name":"Russian Scientific Center of Roentgenoradiology, 117485 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey A.","family":"Kozin","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-1983","authenticated-orcid":false,"given":"Vladimir A.","family":"Mitkevich","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Makarov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Penke, B., Bog\u00e1r, F., and Fulop, L. 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