{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:08:05Z","timestamp":1785294485787,"version":"3.55.0"},"reference-count":62,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Transition metal ions have been implicated in modulation the conformational behavior and aggregation of WT \u03b1\u2010synuclein (WT\u2010\u03b1Syn), associated with Parkinson's disease pathology. Nevertheless, the initial structural rearrangements that drive aggregation are not fully understood. Here, we employed time\u2010resolved small\u2010angle X\u2010ray scattering (TR\u2010SAXS) in a microfluidic setup to investigate the structural dynamics of monomeric WT\u2010\u03b1Syn upon interaction with Mn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , Fe\n                    <jats:sup>3<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    , and Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    . Using Guinier analysis, GNOM, and Ensemble Optimization Method (EOM), we resolved distinct, metal\u2010specific conformational transitions on the sub\u2010second timescale. Fe\n                    <jats:sup>3<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    induced rapid and sustained compaction of \u03b1Syn, while Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    promoted extended and heterogeneous conformations, expanding the C\u2010terminal domain, and disrupting global folding. In contrast, Mn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    and Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    led to more gradual, domain\u2010specific compaction. Fractal dimension analysis and hierarchical clustering further revealed Fe\n                    <jats:sup>3<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    and Zn\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    enriched compaction states, while Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    favored intermediate species potentially linked to early aggregation. These findings highlight how metal ion binding differentially and initially reshape the conformation ensemble of WT\u2010\u03b1Syn, offering mechanistic insight into metal\u2010induced misfolding pathways relevant to synucleinopathies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512293","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:59:32Z","timestamp":1773025172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Time\u2010Resolved SAXS Reveals Distinct Millisecond Metal\u2010Induced Conformational Dynamics of Monomeric \u03b1\u2010Synuclein"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-8244","authenticated-orcid":false,"given":"Rebecca","family":"Sternke\u2010Hoffmann","sequence":"first","affiliation":[{"name":"PSI Center for Life Sciences  Villigen PSI Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Dos Santos","family":"Pinto","sequence":"additional","affiliation":[{"name":"PSI Center for Life Sciences  Villigen PSI Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"PSI Center for Life Sciences  Villigen PSI Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7014-8153","authenticated-orcid":false,"given":"Jinghui","family":"Luo","sequence":"additional","affiliation":[{"name":"PSI Center for Life Sciences  Villigen PSI Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.01.030"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1107\/S205225251500202X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202300110"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CP02001D"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/471151a"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.3c00404"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26409"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9105495"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c02088"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-20164-1_8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.70067"},{"key":"e_1_2_10_13_1","first-page":"299","volume-title":"Small 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