{
  "abstract": "Zinc is essential for life yet toxic in excess, rendering homeostatic control vital for all organisms. Transition metal transporting P-type (PIB-) ATPase proteins are critical for this balance but remain poorly understood at the molecular level. Here, we present the inward-open structure of a dimeric zinc-transporting PIB-type ATPase, resolved at 3.6 Å resolution. Biochemical analyses and molecular dynamics simulations suggest that the N-terminal tail, harboring two so-called metal binding domains (MBDs), auto-inhibits the ATPase core and serves as a metal-sensitive sensor, releasing inhibition when intracellular metal levels rise. Contrary to the prevailing uptake models, the structure reveals an electronegatively charged uptake region that directly exposes a metal-binding cysteine of the invariant CPC-motif. We propose that a histidine-rich segment, positioned after the MBD closest to the core, donates ions to the CPC site. Consequently, an intricate interplay between the regulatory and ion-providing N-terminus and the ATPase core is present, safeguarding against zinc toxicity. Collectively, our findings shed light on the regulation and transport mechanism of PIB-ATPases, with implications for fundamental biology and the potential to inform future biotechnological and translational applications.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.",
    "Department of Chemistry, Umeå University, Umeå, Sweden.",
    "Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, TX, USA.",
    "Department of Experimental Medical Science, Lund University, Lund, Sweden.",
    "Department of Haematology, University of Cambridge, Cambridge, UK.",
    "Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. pontus.gourdon@med.lu.se.",
    "Department of Experimental Medical Science, Lund University, Lund, Sweden. pontus.gourdon@med.lu.se."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pin Lyu"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Longhin"
    },
    {
      "affs": [
        1
      ],
      "name": "Fatemeh Sabzian-Molaei",
      "orcid": "0000-0002-7413-1762"
    },
    {
      "affs": [
        2
      ],
      "name": "Fernando Montalvillo Ortega",
      "orcid": "0009-0008-5041-9930"
    },
    {
      "affs": [
        3
      ],
      "name": "Ping Li",
      "orcid": "0000-0002-7364-3301"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaituo Wang",
      "orcid": "0000-0002-5922-7109"
    },
    {
      "affs": [
        0
      ],
      "name": "Annette Duelli"
    },
    {
      "affs": [
        0
      ],
      "name": "Tamim Al-Jubair"
    },
    {
      "affs": [
        0
      ],
      "name": "Hajira Ahmed Hotiana"
    },
    {
      "affs": [
        0
      ],
      "name": "Eva Ramos Becares"
    },
    {
      "affs": [
        4
      ],
      "name": "Tristan Croll",
      "orcid": "0000-0002-3514-8377"
    },
    {
      "affs": [
        2
      ],
      "name": "Gabriele Meloni",
      "orcid": "0000-0003-4976-1401"
    },
    {
      "affs": [
        1
      ],
      "name": "Magnus Andersson",
      "orcid": "0000-0002-3364-6647"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Viktoria Bågenholm"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Pontus Gourdon",
      "orcid": "0000-0002-8631-3539"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8v80vjvnyh20g.bib",
  "cited_by": 1,
  "doi": "10.1038/s41467-026-77558-1",
  "fulltext_url": "https://europepmc.org/articles/PMC13677743",
  "id": "8v80vjvnyh20g",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894012",
  "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": [
    [
      "openalex",
      "1312|ATP Synthase and ATPases Research"
    ]
  ],
  "openalex": "W7213287787",
  "pdf_url": "https://europepmc.org/articles/PMC13677743?pdf=render",
  "pmcid": "PMC13677743",
  "pmid": "42894012",
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8v80vjvnyh20g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42894012",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894012"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|ATP Synthase and ATPases Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structural and functional insights into a Zn²⁺-transporting P-type ATPase.",
  "title_text": "Structural and functional insights into a Zn²⁺-transporting P-type ATPase.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/8v80vjvnyh20g",
  "venue": "Nature communications",
  "versions": []
}