{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:02:43Z","timestamp":1790074963828,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Biophysics","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["RM1GM149406"],"award-info":[{"award-number":["RM1GM149406"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:p>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 \u03b14. 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 \u03b16\u03b21 integrin. Consistent with structural competition, MCAM occupation of laminin \u03b14 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 \u03b14 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.<\/jats:p>","DOI":"10.64898\/2026.09.11.751044","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:50:14Z","timestamp":1789761014000},"source":"Crossref","is-referenced-by-count":0,"title":["Structural Basis for MCAM Mediated Inhibition of Laminin Dependent Cell Migration"],"prefix":"10.64898","author":[{"given":"Tongqing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Alarcon-Frias","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio R.","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-0450","authenticated-orcid":false,"given":"Daryl E.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092203050801000_2026.09.11.751044v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.024"},{"key":"2026092203050801000_2026.09.11.751044v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.037"},{"key":"2026092203050801000_2026.09.11.751044v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3628"},{"key":"2026092203050801000_2026.09.11.751044v1.4","doi-asserted-by":"crossref","unstructured":"Yurchenco, P.D. , Basement membranes: cell scaffoldings and signaling platforms. 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