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| Title | Three cryo-EM structures of complement C3d-bound alpha M beta 2 reveal an unexpected layer of dynamics for alpha I-containing integrin receptors. |
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| Journal, issue, pages | Sci Adv, Vol. 12, Page eaea7241-eaea7241, Year 2026 |
| Publish date | Aug 29, 2024 (structure data deposition date) |
Authors | Josefine Lorentzen / Marlene Uglebjerg Fruergaard / Szilvia Lukácsi / Martin Høgholm Jørgensen / Timo Lambertus Gerardus van Veghel / Rasmus Kjeldsen Jensen / Krzysztof Jakub Pietrzak-Lichwa / Zsuzsa Bajtay / Václav Hořejší / Rasmus Kock Flygaard / Daan Vorselen / Simon Arnold Mortensen / Gregers Rom Andersen / ![]() |
| PubMed Abstract | Integrins are heterodimeric membrane proteins acting as mechanosensing receptors. Nine human α-subunits contain a ligand binding αI domain, but how ligands activate αI integrins are not understood. ...Integrins are heterodimeric membrane proteins acting as mechanosensing receptors. Nine human α-subunits contain a ligand binding αI domain, but how ligands activate αI integrins are not understood. We present cryo-EM structures of the αI integrin αβ in complex with the C3d ligand. The ligand-bound αI domain appears to have two major opposite orientations relative to the β subunit. Ligand binding induces an ordered conformation of the α internal ligand region that is tightly packed between the α β-propeller and the β βI-domain. Recognition of the internal ligand induces an open βI conformation practically identical to that of ligand-bound αI-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 αβ in the phagocytotic cup and outline mechanistic models for external ligand-induced activation of αβ. |
External links | Sci Adv / PubMed:42102216 / PubMed Central |
| Methods | X-ray diffraction / EM (single particle) |
| Resolution | 2.17 - 3.94 Å |
| Structure data | ![]() PDB-9gmu: ![]() PDB-9hll: ![]() PDB-9rm9: ![]() PDB-9rma: ![]() PDB-9t3y: ![]() PDB-9t5v: ![]() PDB-9t5w: ![]() PDB-9t5z: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-SO4: ![]() ChemComp-HOH: ![]() ChemComp-CA: ![]() ChemComp-NAG: ![]() ChemComp-MN: |
| Source |
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Keywords | IMMUNE SYSTEM / integrin receptor / ligand binding domain / antibody / VHH / complement / phagocytosis / integrin / opsonisation |
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homo sapiens (human)
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