{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:59:00Z","timestamp":1783630740119,"version":"3.55.0"},"reference-count":70,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["Marie Sk\u0142odowska-Curie Innovative Training Network, grant 765048"],"award-info":[{"award-number":["Marie Sk\u0142odowska-Curie Innovative Training Network, grant 765048"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of \u03b1-synuclein (\u03b1S), an intrinsically disordered protein involved in Parkinson\u2019s disease. We perform here a comparative analysis between the structural features of human \u03b1S and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric \u03b1S leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of \u03b1S with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of \u03b1S.<\/jats:p>","DOI":"10.3390\/ijms21145061","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:08:17Z","timestamp":1595225297000},"page":"5061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Role of Tyr-39 for the Structural Features of \u03b1-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly"],"prefix":"10.3390","volume":"21","author":[{"given":"Oscar","family":"Palomino-Hernandez","sequence":"first","affiliation":[{"name":"Computational Biomedicine, Institute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"},{"name":"Faculty of Mathematics, Computer Science and Natural Sciences, RWTH Aachen, 52425 Aachen, Germany"},{"name":"Computation-Based Science and Technology Research Center, The Cyprus Institute, 2121 Nicosia, Cyprus"},{"name":"Institute of Life Science, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiamma A.","family":"Buratti","sequence":"additional","affiliation":[{"name":"Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de F\u00e1rmacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, S2002LRK Rosario, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Sacco","sequence":"additional","affiliation":[{"name":"Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de F\u00e1rmacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, S2002LRK Rosario, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2032-4630","authenticated-orcid":false,"given":"Giulia","family":"Rossetti","sequence":"additional","affiliation":[{"name":"Computational Biomedicine, Institute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"},{"name":"Department of Oncology, Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation University Hospital Aachen, RWTH Aachen University, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"J\u00fclich Supercomputing Center (JSC), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-0149","authenticated-orcid":false,"given":"Paolo","family":"Carloni","sequence":"additional","affiliation":[{"name":"Computational Biomedicine, Institute for Neuroscience and Medicine (INM-9) and Institute for Advanced Simulations (IAS-5), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"},{"name":"Faculty of Mathematics, Computer Science and Natural Sciences, RWTH Aachen, 52425 Aachen, Germany"},{"name":"Institute for Neuroscience and Medicine (INM-11) Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio O.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de F\u00e1rmacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, S2002LRK Rosario, Argentina"},{"name":"Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrn1007","article-title":"Unfolding the role of protein misfolding in neurodegenerative diseases","volume":"4","author":"Soto","year":"2003","journal-title":"Nat. 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