{
  "abstract": "Electrolyte conditions in vivo and in vitro are known to influence protein structure and function. Intrinsically disordered proteins (IDPs) are particularly sensitive to their solution conditions such as ionic strength and molecular crowding, and their dynamic structural ensembles rapidly respond to the cellular environment. While structural mass spectrometry (MS) techniques are uniquely able to capture aspects of this structural diversity, technical limitations have largely precluded the use of native MS approaches to interrogate the conformational rearrangements of IDPs in response to high concentrations of non-volatile salts. Here, we overcome this challenge by employing sub 100-nm nanopipette electrospray emitters for more gentle and salt-tolerant analysis to study the conformational distribution of α-Synuclein (αS) using native MS and ion mobility-MS in varied solution conditions, including in phosphate buffered saline. We show using native MS that it is possible to capture salt and buffer induced changes in the αS conformational ensemble when using traditional biochemical buffers, which reflect structural changes from in silico predictions and in-solution measurements. This work demonstrates the power of nanopipette emitters for the study of IDPs, and establishes native MS as a method that can be routinely used to determine how solution conditions tune the conformational landscape of IDPs.",
  "abstract_shown": true,
  "affiliations": [
    "Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences",
    "University of Leeds",
    "Bragg Centre for Materials Research",
    "School of Electronic and Electrical Engineering",
    "School of Chemistry"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Emily J. Byrd",
      "orcid": "0000-0002-9876-1400"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Emma L. Norgate",
      "orcid": "0000-0002-6787-0268"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Joel A. Crossley",
      "orcid": "0000-0002-6656-1578"
    },
    {
      "affs": [
        2,
        3,
        1
      ],
      "name": "Chalmers Chi Cheng Chau",
      "orcid": "0000-0002-3134-6798"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bob Schiffrin",
      "orcid": "0000-0002-1670-7356"
    },
    {
      "affs": [
        4,
        1
      ],
      "name": "Alexander N. Kulak",
      "orcid": "0000-0002-2798-9301"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sheena E. Radford",
      "orcid": "0000-0002-3079-8039"
    },
    {
      "affs": [
        2,
        3,
        1
      ],
      "name": "Paolo Actis",
      "orcid": "0000-0002-7146-1854"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Antonio N. Calabrese",
      "orcid": "0000-0003-2437-7761"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Frank Sobott",
      "orcid": "0000-0001-9029-1865"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dsxwmj8q9fnyc.bib",
  "cited_by": 6,
  "doi": "10.1021/acs.analchem.6c00544",
  "fulltext_url": null,
  "id": "dsxwmj8q9fnyc",
  "issns": [
    "0003-2700",
    "1520-6882"
  ],
  "landing_url": "https://doi.org/10.1021/acs.analchem.6c00544",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1607|Mass Spectrometry Techniques and Applications"
    ]
  ],
  "openalex": "W7162301718",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acs.analchem.6c00544?ref=article_openPDF",
  "pmcid": "PMC13261622",
  "pmid": "42183579",
  "published": "2026-05-25",
  "publisher": "American Chemical Society",
  "ris": "https://research.draconitic.com/paper/dsxwmj8q9fnyc.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:03Z",
      "native_id": "W7162301718",
      "source": "openalex",
      "url": "https://doi.org/10.1021/acs.analchem.6c00544"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Mass Spectrometry Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Nanopipettes Enable Native Mass Spectrometry Studies of the Intrinsically Disordered Protein α-Synuclein in Biochemical Buffers",
  "title_text": "Nanopipettes Enable Native Mass Spectrometry Studies of the Intrinsically Disordered Protein α-Synuclein in Biochemical Buffers",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:03Z",
  "url": "https://research.draconitic.com/paper/dsxwmj8q9fnyc",
  "venue": "Analytical Chemistry",
  "versions": []
}