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Adv."],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>\n                    Integrins are heterodimeric membrane proteins acting as mechanosensing receptors. Nine human \u03b1-subunits contain a ligand binding \u03b1I domain, but how ligands activate \u03b1I integrins are not understood. We present cryo-EM structures of the \u03b1I integrin \u03b1\n                    <jats:sub>M<\/jats:sub>\n                    \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    in complex with the C3d ligand. The ligand-bound \u03b1I domain appears to have two major opposite orientations relative to the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    subunit. Ligand binding induces an ordered conformation of the \u03b1\n                    <jats:sub>M<\/jats:sub>\n                    internal ligand region that is tightly packed between the \u03b1\n                    <jats:sub>M<\/jats:sub>\n                    \u03b2-propeller and the \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2I-domain. Recognition of the internal ligand induces an open \u03b2I conformation practically identical to that of ligand-bound \u03b1I-less integrins confirming that ligand binding and signaling are coupled by a universal mechanism across all integrins. Integration of our findings with prior data allows us to propose a model for C3dg\/iC3b-bound \u03b1\n                    <jats:sub>M<\/jats:sub>\n                    \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    in the phagocytotic cup and outline mechanistic models for external ligand-induced activation of \u03b1\n                    <jats:sub>M<\/jats:sub>\n                    \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    .\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea7241","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:53:19Z","timestamp":1778579599000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Three cryo-EM structures of complement C3d-bound \u03b1\n                    <sub>M<\/sub>\n                    \u03b2\n                    <sub>2<\/sub>\n                    reveal an unexpected layer of dynamics for \u03b1I-containing integrin receptors"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-2168","authenticated-orcid":true,"given":"Josefine","family":"Lorentzen","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, Aarhus, DK8000, Denmark."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlene Uglebjerg","family":"Fruergaard","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Aarhus University, Aarhus, DK8000, Denmark."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3499-8422","authenticated-orcid":true,"given":"Szilvia","family":"Luk\u00e1csi","sequence":"additional","affiliation":[{"name":"MTA-ELTE Immunology Research Group, E\u00f6tv\u00f6s Lor\u00e1nd Research Network (ELKH), E\u00f6tv\u00f6s Lor\u00e1nd University, Budapest, H-1117, 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