8S3O
Structure of native human CD109
Summary for 8S3O
| Entry DOI | 10.2210/pdb8s3o/pdb |
| EMDB information | 19699 |
| Descriptor | CD109 antigen, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | protease inhibitor, native conformation, alfa-macroglobulin, immune system |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 163584.76 |
| Authors | Almeida, V.A.,Andersen, G.R. (deposition date: 2024-02-20, release date: 2025-03-05, Last modification date: 2025-09-17) |
| Primary citation | Almeida, A.V.,Jensen, K.T.,Harwood, S.L.,Jorgensen, M.H.,Nielsen, N.S.,Thogersen, I.B.,Enghild, J.J.,Andersen, G.R. Three cryo-EM structures of CD109 reveal its mechanism of protease inhibition. Cell Rep, 44:115787-115787, 2025 Cited by PubMed Abstract: CD109 is a glycosylphosphatidylinositol-anchored protein. In addition to regulating transforming growth factor β (TGF-β) network signaling, CD109 is also a protease inhibitor. Protease cleavage of its bait region triggers a conformational change releasing the major fragment from the cell surface, exposing a reactive thioester that can conjugate proteases. To understand this protease inhibition mechanism, we determined cryoelectron microscopy structures of CD109 in native, protease-activated, and methylamine-activated conformations. Despite CD109's low sequence similarity with the protease inhibitor A2ML1, CD109 adopts a similar protease-activated conformation, suggesting a shared mechanism of protease inhibition. Deglycosylation of CD109 does not affect chymotrypsin conjugation but enhances substrate access, suggesting that CD109 glycans contribute to protease inhibition. Our data provide a structural basis for understanding CD109's protease-triggered membrane release, its protease inhibitory mechanism, and additional biological functions. PubMed: 40482031DOI: 10.1016/j.celrep.2025.115787 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.99 Å) |
Structure validation
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