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The unresolved N\u2010 and C\u2010terminal segments form a fuzzy coat that is expected to shape the surface encountered by molecular partners. Here, we reconstructed full\u2010length, brain\u2010derived aSyn Lewy\u2010fold fibrils by extending a patient\u2010derived cryo\u2010EM core spanning residues 31\u2013100, with disordered termini, and sampling the resulting assemblies with the CALVADOS coarse\u2010grained force field. The acidic C\u2010terminal tails established recurrent, transient contacts with solvent\u2010exposed core motifs, especially \u03b25\/P2 and \u03b29\/P3, generating a dynamic surface in which aggregation\u2010prone ladders are intermittently shielded rather than permanently buried. Simulations with two experimentally validated aSyn\u2010binding peptides, PSM\u03b13 and LL\u201037, show that peptide recognition follows a two\u2010step process. Cationic peptides are first retained by the anionic fuzzy coat and subsequently engage exposed hydrophobic\/electrostatic hotspots on the structured core. PSM\u03b13 variants and LL\u201037 controls support the importance of positive charge for capture, peptide flexibility for multivalent engagement, and the full\u2010length fibril architecture for persistent binding. These results present a mechanistic model in which selectivity for aggregated aSyn arises from an emergent mesoscale interface combining a polyelectrolyte brush with recurrent core hotspots. Together, these results establish full\u2010length, brain\u2010derived fibril ensembles as a practical framework for understanding ligand recognition at amyloid surfaces.<\/jats:p>","DOI":"10.1002\/pro.70782","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:46:26Z","timestamp":1789469186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Full\u2010length brain\u2010derived \u03b1\u2010synuclein fibril models reveal fuzzy\u2010coat control of peptide recognition"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-959X","authenticated-orcid":false,"given":"Carlos","family":"Pintado\u2010Grima","sequence":"first","affiliation":[{"name":"Institut de Biotecnologia i de Biomedicina and Departament de Bioqu\u00edmica i Biologia Molecular Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8439-4005","authenticated-orcid":false,"given":"Oriol","family":"B\u00e1rcenas","sequence":"additional","affiliation":[{"name":"Institut de Biotecnologia i de Biomedicina and Departament de Bioqu\u00edmica i Biologia Molecular Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Institute of Advanced Chemistry of Catalonia (IQAC) CSIC  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-4460","authenticated-orcid":false,"given":"Giulio","family":"Tesei","sequence":"additional","affiliation":[{"name":"Linderstr\u00f8m\u2010Lang Centre for Protein Science, Department of Biology University of Copenhagen  Copenhagen N Denmark"},{"name":"Department of Biomedical Science Malm\u00f6 University  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-4873","authenticated-orcid":false,"given":"F. 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