{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:32:01Z","timestamp":1793399521232,"version":"4.5.0"},"posted":{"date-parts":[[2025,7,20]]},"group-title":"Biochemistry","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Research Foundation - Flanders","award":["12AWB24N"],"award-info":[{"award-number":["12AWB24N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Research Foundation - Flanders","award":["G0C3522N"],"award-info":[{"award-number":["G0C3522N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"crossref"}]},{"award":["R01AG079234"],"award-info":[{"award-number":["R01AG079234"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Munich Cluster for Systems Neurology","award":["EXC 2145 SyNergy\u2013ID 390857198"],"award-info":[{"award-number":["EXC 2145 SyNergy\u2013ID 390857198"]}],"id":[{"id":"https:\/\/ror.org\/025z3z560","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Amyloid assembly in vivo occurs in complex proteomic environments where multiple aggregation-prone species coexist. A\u03b2 and medin are two highly prevalent amyloids in ageing humans, and medin co-localizes with A\u03b2 in cerebral amyloid angiopathy (CAA). Yet the structural consequences of their interaction remain unclear. Here, we determine the cryo-electron microscopy (cryo-EM) structures of fibrils formed from defined in vitro mixtures of A\u03b240 and medin. From the same reaction, we resolve three fibril populations: (i) a previously described A\u03b240 polymorph that also forms in isolation, (ii) a novel A\u03b240 polymorph with A\u03b242-like features, including ordered N- and C-terminal regions, and (iii) the first atomic structure of full-length medin fibrils. Biochemical and immunogold analyses demonstrate association between A\u03b2 and medin within the mixed assemblies. However, the cryo-EM map of the novel A\u03b2 polymorph does not unambiguously resolve medin within the ordered A\u03b2 core. These findings are consistent with two non-exclusive mechanisms by which the polymorphic landscape is reshaped in mixtures: transient heterotypic amyloid interactions that redirect A\u03b2 folding pathways, or partial and structurally heterogeneous incorporation of medin into the fibril architecture. Regardless of the precise structural mechanism, our data demonstrate that interactions between coexisting amyloids can remodel their polymorphic landscape, revealing how mixed amyloid systems generate emergent conformations.<\/jats:p>","DOI":"10.1101\/2025.07.17.665283","type":"posted-content","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T04:05:14Z","timestamp":1753070714000},"source":"Crossref","is-referenced-by-count":4,"title":["Atomic structures of medin and A\u03b2 fibrils reveal polymorphic remodeling in mixed amyloid systems"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5732-6675","authenticated-orcid":false,"given":"Brajabandhu","family":"Pradhan","sequence":"first","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-3963","authenticated-orcid":false,"given":"Senthil T","family":"Kumar","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8585-6998","authenticated-orcid":false,"given":"Jessica","family":"Wagner","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Biochemistry, Faculty of Medicine, LMU Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1584-3564","authenticated-orcid":false,"given":"Rodrigo","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5935-5258","authenticated-orcid":false,"given":"Gabriele","family":"Orlando","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-1928","authenticated-orcid":false,"given":"Matthias De","family":"Vleeschouwer","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-309X","authenticated-orcid":false,"given":"Valentina","family":"zorzini","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9963-5871","authenticated-orcid":false,"given":"Jillian","family":"Madine","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular & Integrative Biology, University of Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-1022","authenticated-orcid":false,"given":"Nikolas","family":"Louros","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1346-8924","authenticated-orcid":false,"given":"Jonas J.","family":"Neher","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Biochemistry, Faculty of Medicine, LMU Munich, Munich, Germany"},{"name":"Neuroimmunology and Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany"},{"name":"Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-7399","authenticated-orcid":false,"given":"Frederic","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-0168","authenticated-orcid":false,"given":"Joost","family":"Schymkowitz","sequence":"additional","affiliation":[{"name":"Switch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, 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