{
  "abstract": "Copper–cysteine (Cu–Cys) coordination is pervasive in biology, yet how Cu–thiol redox chemistry engages O2 and translates into protein-level consequences remains incompletely understood. Here, we establish a generalizable protein-based platform that directly captures O2-coupled Cu(II)–Cys redox processes and delineates their structural and functional outcomes. Integrated spectroscopic, mass spectrometric, and computational investigations reveal that Cu(II) coordination to a protein Cys residue initiates redox cycling that generates thiyl radicals and/or disulfide radical anions. This chemically defined process drives disulfide bond formation together with O2-dependent oxidative transformations, producing site-specific Cys modifications, dityrosine cross-links, and higher-order protein assemblies. Under these conditions, these structural changes abolish the protein’s anti-amyloidogenic activity and result in apoptotic responses. By directly linking Cu–thiol redox chemistry to protein oxidation and aggregation, this work establishes a fundamental chemical principle by which redox-active metal ions govern protein fate under aerobic conditions. More broadly, these findings provide a mechanistic framework for understanding how metal-mediated oxidative chemistry contributes to protein misfolding and aggregation in human diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Korea Advanced Institute of Science and Technology (KAIST) , , ,",
    "Daegu Gyeongbuk Institute of Science and Technology (DGIST) , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yelim Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Wooyeol Ryu"
    },
    {
      "affs": [
        1
      ],
      "name": "Bokyung Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Srinivasan Muniyappan"
    },
    {
      "affs": [
        1
      ],
      "name": "Jin Hae Kim",
      "orcid": "0000-0002-6776-2451"
    },
    {
      "affs": [
        0
      ],
      "name": "Kiyoung Park",
      "orcid": "0000-0001-9323-7979"
    },
    {
      "affs": [
        0
      ],
      "name": "Mi Hee Lim",
      "orcid": "0000-0003-3377-4996"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eatenwvrjqxrm.bib",
  "cited_by": 0,
  "doi": "10.1021/acscentsci.6c00619",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720927/?tool=EBI",
  "id": "eatenwvrjqxrm",
  "issns": [
    "2374-7943",
    "2374-7951"
  ],
  "landing_url": "https://pubs.acs.org/acscii/article/12/10/1659/5444810/O2-Coupled-Copper-Cysteine-Redox-Chemistry-Drives",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Redox biology and oxidative stress"
    ]
  ],
  "openalex": "W7220470353",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00619",
  "pmcid": "PMC13720927",
  "pmid": "42965001",
  "published": "2026-10-05",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/eatenwvrjqxrm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:37Z",
      "native_id": "10.1021/acscentsci.6c00619",
      "source": "crossref",
      "url": "https://pubs.acs.org/acscii/article/12/10/1659/5444810/O2-Coupled-Copper-Cysteine-Redox-Chemistry-Drives"
    },
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13720927",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13720927"
    },
    {
      "first_seen": "2026-11-03T12:21:43Z",
      "native_id": "PMC13720927",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acscentsci.6c00619"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "O2-Coupled Copper–Cysteine Redox Chemistry Drives Oxidative Modifications and Higher-Order Assembly of Monomeric Transthyretin",
  "title_text": "O2-Coupled Copper–Cysteine Redox Chemistry Drives Oxidative Modifications and Higher-Order Assembly of Monomeric Transthyretin",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:43Z",
  "url": "https://research.draconitic.com/paper/eatenwvrjqxrm",
  "venue": "ACS Central Science",
  "versions": []
}