{
  "abstract": "MCAM/CD146 is an immunoglobulin-superfamily receptor expressed on endothelial cells, immune cells and numerous carcinomas. Although MCAM has long been associated with metastatic progression, recent work has revealed context-dependent inhibitory effects on transendothelial migration, leaving unresolved how MCAM engagement of basement membrane laminins alters cell migration. Here, we report multiple cryo-electron microscopy structures of human MCAM bound to laminin. We show MCAM engages laminin on a surface centered on the first two laminin globular domains (LG1-2) and that this epitope directly overlaps with the interface used by integrin. Consistent with structural competition, MCAM occupation of laminin abolishes integrin-dependent cell migration. Structure-guided mutation of the MCAM-laminin interface disrupts laminin binding and eliminates MCAM-mediated inhibition. These findings establish that MCAM and integrin compete for a shared interface on laminin and define a structural mechanism by which MCAM occupancy can suppress laminin-dependent migration. The structure resolves a central ambiguity in MCAM biology and provides a framework for developing biologics that selectively modulate pathological cell migration.",
  "abstract_shown": true,
  "affiliations": [
    "Yale University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "D. E. Klein"
    },
    {
      "name": "T. Li"
    },
    {
      "name": "S. Alarcon-Frias"
    },
    {
      "name": "H. Li"
    },
    {
      "name": "C. Alarcon"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fnjpdzbrbxjsn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.11.751044",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751044v1.full",
  "id": "fnjpdzbrbxjsn",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751044v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "2723|Cell Adhesion Molecules Research"
    ]
  ],
  "openalex": "W7213549205",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751044v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fnjpdzbrbxjsn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:06Z",
      "native_id": "10.64898/2026.09.11.751044",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.11.751044v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Structural Basis for MCAM Mediated Inhibition of Laminin Dependent Cell Migration",
  "title_text": "Structural Basis for MCAM Mediated Inhibition of Laminin Dependent Cell Migration",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:06Z",
  "url": "https://research.draconitic.com/paper/fnjpdzbrbxjsn",
  "venue": "bioRxiv",
  "versions": []
}