{
  "abstract": "Membranes are central to both the physiological and pathological roles of α-synuclein (αSyn). Here, we define the roles of exons 3 and 5 of αSyn in membrane interactions and determine how alternative splicing influences membrane binding, protein conformation, membrane remodelling and lipid-induced amyloid formation. We show that deletion of residues encoded by exon 3 reduces membrane-bound helicity to a greater extent than expected from the loss of those residues alone, diminishes the ability of αSyn to lower the membrane gel-to-fluid transition temperature (T m), and shifts membrane remodelling behaviour from tubulation to fission. Conversely, deletion of exon 5-encoded residues has little effect on membrane affinity, membrane-induced helix formation, modulation of liposomal T m, or membrane remodelling activity. Despite this, deletions of these residues play a key role in determining the flux through different pathways for lipid-induced amyloid formation, resulting in the formation of structurally distinct fibril populations. Thus, exons 3 and 5 make mechanistically distinct contributions to the relationship between αSyn and membranes with different effects on protein conformation and aggregation. Together, these findings demonstrate that alternative splicing remodels the interplay between αSyn, membranes, and amyloid formation. Mapping the sequence determinants that underlie these processes provides insight into how alternative splicing changes both the physiological functions of αSyn and its involvement in disease.",
  "abstract_shown": true,
  "affiliations": [
    "Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Health and Life Sciences, University of Leeds Leeds LS2 9JT UK."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Katherine M Dewison",
      "orcid": "0000-0002-7196-7687"
    },
    {
      "affs": [
        0
      ],
      "name": "Pijush Chakraborty",
      "orcid": "0000-0003-1749-5225"
    },
    {
      "affs": [
        0
      ],
      "name": "David J Brockwell",
      "orcid": "0000-0002-0802-5937"
    },
    {
      "affs": [
        0
      ],
      "name": "Sheena E Radford",
      "orcid": "0000-0002-3079-8039"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/arq547pbxf7ff.bib",
  "cited_by": 0,
  "doi": "10.1039/d6sc07425a",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13726718/?tool=EBI",
  "id": "arq547pbxf7ff",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13726718",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7224143524",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13726718/pdf/?tool=EBI",
  "pmcid": "PMC13726718",
  "pmid": "42974245",
  "published": "2026-11-02",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/arq547pbxf7ff.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC13726718",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13726718"
    },
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42974245",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974245"
    },
    {
      "first_seen": "2026-11-05T12:23:00Z",
      "native_id": "PMC13726718",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6sc07425a"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "The cassette exons of α-synuclein play distinct roles in membrane remodelling and membrane-mediated amyloid formation",
  "title_text": "The cassette exons of α-synuclein play distinct roles in membrane remodelling and membrane-mediated amyloid formation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:36Z",
  "url": "https://research.draconitic.com/paper/arq547pbxf7ff",
  "venue": "Chemical science",
  "versions": []
}