{
  "abstract": "Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a general deep learning–based design approach for solubilizing native membrane proteins while preserving their sequence, fold, active-site, and ligand-binding properties. Genetically encoded de novo protein WRAPs [water-soluble RFdiffused amphipathic proteins] surround the lipid-interacting hydrophobic surfaces, rendering them thermostable and water-soluble without the need for detergents. We design WRAPs for both monomeric and oligomeric beta-barrel outer membrane proteins and helical multipass transmembrane proteins. A 2.95-angstrom-resolution cryo–electron microscopy structure of WRAPed mycobacterial porin demonstrates that WRAPs can be used for the structural determination of membrane proteins in solution. As a step toward syphilis vaccine development, we generated soluble versions of Treponema pallidum antigens.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry, Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.",
    "Department of Pediatrics, UConn Health, Farmington, CT 06030-3715, USA.",
    "Kymab, a Sanofi Company, Babraham Research Campus, Cambridge, UK.",
    "Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington",
    "Department of Cell and Molecular Biology, Uppsala University, 751 24 Uppsala, Sweden",
    "Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ljubica Mihaljević"
    },
    {
      "affs": [
        0
      ],
      "name": "David E. Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Pooja D. Bandawane"
    },
    {
      "affs": [
        0
      ],
      "name": "Helen E. Eisenach"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrew J. Borst"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexis Courbet"
    },
    {
      "affs": [
        0
      ],
      "name": "Connor Weidle"
    },
    {
      "affs": [
        0
      ],
      "name": "Kenneth D. Carr"
    },
    {
      "affs": [
        1
      ],
      "name": "Everton Bettin"
    },
    {
      "affs": [
        2
      ],
      "name": "Qiushi Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Aldo T. Trejos"
    },
    {
      "affs": [
        0
      ],
      "name": "Sagardip Majumder"
    },
    {
      "affs": [
        4
      ],
      "name": "Surabhi Kokane"
    },
    {
      "affs": [
        4
      ],
      "name": "Alexander Stevens"
    },
    {
      "affs": [
        0
      ],
      "name": "Edin Muratspahić"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas Schlichthaerle"
    },
    {
      "affs": [
        0
      ],
      "name": "Marc Expòsit"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinting Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Mila Lamb"
    },
    {
      "affs": [
        0
      ],
      "name": "Analisa Nicole Azcárraga Murray"
    },
    {
      "affs": [
        0
      ],
      "name": "Rashmi Ravichandran"
    },
    {
      "affs": [
        0
      ],
      "name": "Elizabeth C. Williams"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuyuan Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lynda Stuart"
    },
    {
      "affs": [
        5
      ],
      "name": "Linda Grillová"
    },
    {
      "affs": [
        5
      ],
      "name": "Nicholas R. Thomson"
    },
    {
      "affs": [
        4
      ],
      "name": "Michael Landreh"
    },
    {
      "affs": [
        2
      ],
      "name": "Pengxiang Chang"
    },
    {
      "affs": [
        3
      ],
      "name": "Lorenzo Giacani"
    },
    {
      "affs": [
        1
      ],
      "name": "Melissa J. Caimano"
    },
    {
      "affs": [
        1
      ],
      "name": "Kelly L. Hawley"
    },
    {
      "affs": [
        0
      ],
      "name": "Neil P. King"
    },
    {
      "affs": [
        0
      ],
      "name": "David Baker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bn4r477vqdemd.bib",
  "cited_by": 7,
  "doi": "10.1126/science.adr3817",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730216/?tool=EBI",
  "id": "bn4r477vqdemd",
  "issns": [
    "0036-8075",
    "1095-9203"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13730216",
  "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",
      "Article"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7167011808",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730216/pdf/?tool=EBI",
  "pmcid": "PMC13730216",
  "pmid": "42391386",
  "published": "2026-07-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bn4r477vqdemd.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "PMC:PMC13730216",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13730216"
    },
    {
      "first_seen": "2026-11-07T12:22:49Z",
      "native_id": "PMC13730216",
      "source": "pmc",
      "url": "https://doi.org/10.1126/science.adr3817"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Membrane protein solubilization and structure determination using de novo–designed proteins",
  "title_text": "Membrane protein solubilization and structure determination using de novo–designed proteins",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:49Z",
  "url": "https://research.draconitic.com/paper/bn4r477vqdemd",
  "venue": "Science (New York, N.Y.)",
  "versions": []
}