8OXV
Transglutaminase 3 zymogen in complex with DH patient-derived Fab DH63-B02
Summary for 8OXV
| Entry DOI | 10.2210/pdb8oxv/pdb |
| Descriptor | Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain, Antibody Fab fragment Heavy chain, Antibody Fab fragment light chain, ... (7 entities in total) |
| Functional Keywords | transglutaminase, tgm3, tg3, transglutaminase 3, enzyme, zymogen, antibody, dermatitis herpetiformis, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 124310.81 |
| Authors | Heggelund, J.E.,Sollid, L.M. (deposition date: 2023-05-02, release date: 2023-10-18, Last modification date: 2024-11-13) |
| Primary citation | Heggelund, J.E.,Das, S.,Stamnaes, J.,Iversen, R.,Sollid, L.M. Autoantibody binding and unique enzyme-substrate intermediate conformation of human transglutaminase 3. Nat Commun, 14:6216-6216, 2023 Cited by PubMed Abstract: Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either transamidation or deamidation modifications. To become catalytically active TG3 requires proteolytic cleavage between the core domain and two C-terminal β-barrels (C1C2). Here, we report four X-ray crystal structures representing inactive and active conformations of human TG3 in complex with a TG3-specific Fab fragment of a DH patient derived antibody. We demonstrate that cleaved TG3, upon binding of a substrate-mimicking inhibitor, undergoes a large conformational change as a β-sheet in the catalytic core domain moves and C1C2 detaches. The unique enzyme-substrate conformation of TG3 without C1C2 is recognized by DH autoantibodies. The findings support a model where B-cell receptors of TG3-specific B cells bind and internalize TG3-gluten enzyme-substrate complexes thereby facilitating gluten-antigen presentation, T-cell help and autoantibody production. PubMed: 37798283DOI: 10.1038/s41467-023-42004-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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