{
  "abstract": "The protein -synuclein (-syn) plays a central role in several neurodegenerative diseases, including Parkinson's disease; however, its physiological function remains enigmatic. We provide direct evidence by nuclear magnetic resonance (NMR) spectroscopy, microscale thermophoresis (MST), and biolayer interferometry (BLI) measurements that the -synuclein C-terminus binds to the vesicular SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein synaptobrevin-2 (syb-2), also known as VAMP2 (vesicle-associated membrane protein). The observed dissociation constant (Kd) in the 10 - 50 micromolar range falls within the estimated concentration range of -synuclein in neurons, while local concentrations may be substantially higher. NMR chemical shift perturbation (CSP) and paramagnetic relaxation enhancement (PRE) experiments mapped the binding site with residue-specific resolution to the -synuclein C-terminus (V118 - E137) and to the synaptobrevin-2 SNARE motif/linker domain interface (region A82 - K87), and also affected the synaptobrevin-2 N-terminus (M1 - S2). NMR CSPs and PREs indicate a transient interaction in the fast exchange (s-ms) regime. These transient weak binding interactions are characteristic of intrinsically disordered proteins (IDPs) and allow both proteins to engage in multiple binding interactions, thereby enabling -synuclein to play a regulatory role upstream of or during neuronal exocytosis. While the exact physiological role of -synuclein remains debated, the involvement of its pathological form in several neurodegenerative diseases (dubbed synucleinopathies) is well established. Our data suggest a direct link between proteins involved in neurodegeneration and neuronal exocytosis.",
  "abstract_shown": true,
  "affiliations": [
    "Forschungszentrum Julich"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "S. Werner"
    },
    {
      "name": "T. Stief"
    },
    {
      "name": "C. M. Schulz"
    },
    {
      "name": "K. Vormann"
    },
    {
      "name": "R. Backer"
    },
    {
      "name": "M. P. Schutzmann"
    },
    {
      "name": "L. Gremer"
    },
    {
      "name": "W. Hoyer"
    },
    {
      "affs": [
        0
      ],
      "name": "N.-A. Lakomek"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ekc59seqkf8t7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.764002",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764002v1.full",
  "id": "ekc59seqkf8t7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764002v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764002v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ekc59seqkf8t7.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T00:22:03Z",
      "native_id": "10.64898/2026.11.03.764002",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.764002v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Direct NMR evidence for transient binding of the vesicular SNARE protein synaptobrevin-2/VAMP2 to the α-synuclein C-terminus",
  "title_text": "Direct NMR evidence for transient binding of the vesicular SNARE protein synaptobrevin-2/VAMP2 to the α-synuclein C-terminus",
  "type": "preprint",
  "updated_at": "2026-11-05T12:20:37Z",
  "url": "https://research.draconitic.com/paper/ekc59seqkf8t7",
  "venue": "bioRxiv",
  "versions": []
}