9T5Z

Cryo-EM structure of alphaM/beta2:MEM148-Fab headpiece complex (without alphaM I-domain)

Summary for 9T5Z

• Entry DOI: 10.2210/pdb9t5z/pdb
• EMDB information: 55599
• Descriptor: Integrin alpha-M, 2-acetamido-2-deoxy-beta-D-glucopyranose, Integrin beta-2, ... (11 entities in total)
• Functional Keywords: phagocytosis, integrin, opsonisation, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 187462.40

Authors

Lorentzen, J.,Andersen, G.R. (deposition date: 2025-11-06, release date: 2026-03-25, Last modification date: 2026-07-01)

Primary citation

Lorentzen, J.,Fruergaard, M.U.,Lukacsi, S.,Jorgensen, M.H.,van Veghel, T.L.G.,Jensen, R.K.,Pietrzak-Lichwa, K.J.,Bajtay, Z.,Horejsi, V.,Flygaard, R.K.,Vorselen, D.,Mortensen, S.A.,Andersen, G.R.
Three cryo-EM structures of complement C3d-bound alpha M beta 2 reveal an unexpected layer of dynamics for alpha I-containing integrin receptors.
Sci Adv, 12:eaea7241-eaea7241, 2026

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. 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.

PubMed: 42102216
DOI: 10.1126/sciadv.aea7241

Experimental method

ELECTRON MICROSCOPY (3.1 Å)