{
  "abstract": "Microtubules (MTs) are dynamic cytoskeletal polymers whose lattice architecture regulates force generation, nucleotide hydrolysis, and recognition by motor proteins and microtubule-associated proteins (MAPs). Microtubule-stabilizing agents (MSAs), including taxanes and laulimalide/peloruside-site ligands, suppress depolymerization by binding to defined lattice sites, yet stabilization is not structurally neutral. How ligand chemistry reshapes lattice organization and function remains unresolved. Here, we address three mechanistic questions. First, do distinct ligand classes induce defined lattice states? Using X-ray fiber diffraction, we show that MSAs selectively stabilize two preferred longitudinal conformations, a compact state (∼4.06 nm monomer rise) and an expanded state (∼4.17 nm), while modulating lateral organization reflected in shifts in mean MT radius. These axial spacings cluster around discrete values across chemotypes, indicating stabilization of pre-existing conformational minima rather than continuous distortion. Second, are these states interconvertible upon changes in ligand occupancy? Time-resolved diffraction reveals that longitudinal transitions occur within seconds of ligand addition even at substoichiometric occupancy; whereas, lateral equilibration proceeds slower, consistent with redistribution within heterogeneous protofilament organizations. Third, do such structural states alter nucleotide hydrolysis and motor/MAP behavior? Expanded lattices are associated with reduced apparent GTP hydrolysis rates under steady-state assembly conditions and altered kinesin motility, whereas compact lattices preferentially promote tau binding and distinct motor interaction profiles. Together, these findings establish longitudinal lattice conformation as a regulatory parameter and position microtubule-stabilizing agents as chemical tools that bias a dynamic structural landscape with predictable catalytic and transport consequences. Significance statement Microtubules generate force and support intracellular transport through lattice geometries selectively recognized by motor proteins and microtubule-associated proteins. Microtubule-stabilizing drugs such as taxanes and epothilones are widely used in chemotherapy but can cause neurotoxicity, likely because stabilization alters lattice architecture rather than simply preventing depolymerization. Here, we show that stabilizing ligands bias microtubules between two preferred longitudinal conformations, compact and expanded, that can switch within seconds of binding, while lateral organization adjusts slower. These structural states differentially regulate GTP hydrolysis and recognition by tau and kinesin, linking lattice geometry to catalytic and transport functions. By establishing lattice conformation as a tunable regulatory parameter, this work provides a framework for interpreting drug effects and designing structure-selective stabilizers with improved therapeutic profiles.",
  "abstract_shown": true,
  "affiliations": [
    "Unidad Interdepartamental de Desarrollo de Nuevos Fármacos Biológicos, Inmunológicos y Químicos para la Salud Global, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas",
    "Center for Biological Research. CSIC",
    "Centro de Investigaciones Biológicas Margarita Salas",
    "Instituto Madrileño de Estudios Avanzados en Nanociencia",
    "IMDEA-Nanociencia",
    "Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute",
    "Paul Scherrer Institute, Villigen,",
    "Institute of Biotechnology Czech Academy of Sciences, Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University",
    "Institute of Biotechnology of the Czech Academy of Sciences",
    "Centro de Investigaciones Biologicas Margarita Salas",
    "Department of Biological Sciences, Graduate School of Science, The University of Osaka",
    "Osaka University",
    "Department of Life Sciences, Faculty of Biological Resources, Prefectural University of Hiroshima",
    "Faculty of Biological Resources, Prefectural University of Hiroshima",
    "Research and Utilization Division, Japan Synchrotron Radiation Research Institute, SPring-8",
    "Japan Synchrotron Radiation Research Institute",
    "ALBA Synchrotron, Consorcio para la Construcción, Equipamiento y Explotación del Laboratorio de Luz de Sincrotrón",
    "ALBA Synchrotron, CELLS",
    "Ferrier Research Institute, and Centre for Biodiscovery, Victoria University of Wellington",
    "School of Chemical and Physical Sciences, and Centre for Biodiscovery, Victoria University of Wellington",
    "School of Chemical & Physical Sciences, and Centre for Biodiscovery, Victoria University of Wellington",
    "Department of Chemistry, 1102 Natural Sciences II, University of California",
    "Department of Pharmaceutical Sciences, University of California",
    "University of California",
    "ETH Zurich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences",
    "ETH Zurich",
    "Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University",
    "University of Ghent",
    "Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College",
    "Institute of Materia Medica, Beijing",
    "Department of Biomedical Sciences, University of Alcalá",
    "Universidad de Alcala",
    "Institute of Biotechnology CAS, Centrum BIOCEV",
    "Department of Biological Sciences, Faculty of Fundamental Science and Engineering, Chuo University",
    "Chuo University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniel Lucena‐Agell",
      "orcid": "0000-0001-7314-8696"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Óscar Fernández",
      "orcid": "0000-0003-3696-789X"
    },
    {
      "affs": [
        3,
        0,
        4
      ],
      "name": "Rebeca París-Ogáyar",
      "orcid": "0000-0002-7953-0949"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Juan Estévez‐Gallego",
      "orcid": "0000-0003-3889-8488"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Denisa Ondruskova",
      "orcid": "0009-0004-1255-6302"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Beatriz Álvarez-Bernad"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Francesca Bonato",
      "orcid": "0000-0002-0579-2874"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Jaime Larraga",
      "orcid": "0000-0001-7293-7239"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "D. Ortiz de Elguea",
      "orcid": "0009-0002-7334-8983"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Gregorio Javier Cano",
      "orcid": "0009-0008-0645-6320"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Marvin Scheers",
      "orcid": "0009-0003-6922-888X"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Hiroshi Imai",
      "orcid": "0000-0001-8939-2255"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "Toshiki Yagi",
      "orcid": "0000-0002-1379-460X"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Hiroyuki Iwamoto",
      "orcid": "0000-0002-4980-8495"
    },
    {
      "affs": [
        16,
        17
      ],
      "name": "Juan Carlos Martínez-Guil",
      "orcid": "0000-0003-2411-5446"
    },
    {
      "affs": [
        18
      ],
      "name": "A. Jonathan Singh",
      "orcid": "0000-0003-1722-066X"
    },
    {
      "affs": [
        19,
        20
      ],
      "name": "Robert A. Keyzers",
      "orcid": "0000-0002-7658-7421"
    },
    {
      "affs": [
        21,
        22,
        23
      ],
      "name": "Christopher D. Vanderwal",
      "orcid": "0000-0001-7218-4521"
    },
    {
      "affs": [
        24,
        25
      ],
      "name": "Karl‐Heinz Altmann",
      "orcid": "0000-0002-0747-9734"
    },
    {
      "affs": [
        26,
        27
      ],
      "name": "Johan Van der Eycken",
      "orcid": "0000-0002-1623-6750"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Valle Palomo",
      "orcid": "0000-0002-1473-4086"
    },
    {
      "affs": [
        28,
        29
      ],
      "name": "Wei-Shuo Fang"
    },
    {
      "affs": [
        30,
        31
      ],
      "name": "Federico Gago",
      "orcid": "0000-0002-3071-4878"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Zdeněk Lánský",
      "orcid": "0000-0001-8474-053X"
    },
    {
      "affs": [
        7,
        32
      ],
      "name": "Marcus Braun",
      "orcid": "0000-0003-2026-2238"
    },
    {
      "affs": [
        0,
        32
      ],
      "name": "María A. Oliva",
      "orcid": "0000-0002-2215-4639"
    },
    {
      "affs": [
        33,
        34
      ],
      "name": "Shinji Kamimura",
      "orcid": "0000-0003-4359-0859"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "José Fernando Díaz",
      "orcid": "0000-0003-2743-3319"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8mbnv0vm4985n.bib",
  "cited_by": 9,
  "doi": "10.1073/pnas.2532791123",
  "fulltext_url": null,
  "id": "8mbnv0vm4985n",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2532791123",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Microtubule and mitosis dynamics"
    ]
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  "openalex": "W4416225990",
  "pdf_url": null,
  "pmcid": "PMC13291687",
  "pmid": "42301786",
  "published": "2026-06-16",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/8mbnv0vm4985n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W4416225990",
      "source": "openalex",
      "url": "https://doi.org/10.1073/pnas.2532791123"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Microtubule and mitosis dynamics",
      "subfield": "cell-biology"
    }
  ],
  "title": "An atlas of microtubule lattice parameters regulated through ligand binding to the microtubule-stabilizing sites",
  "title_text": "An atlas of microtubule lattice parameters regulated through ligand binding to the microtubule-stabilizing sites",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:30Z",
  "url": "https://research.draconitic.com/paper/8mbnv0vm4985n",
  "venue": "Proceedings of the National Academy of Sciences",
  "versions": []
}