8RMX
Transglutaminase 3 in complex with DH patient-derived Fab DH63-A02
Summary for 8RMX
| Entry DOI | 10.2210/pdb8rmx/pdb |
| Related | 8RMY |
| Descriptor | Protein-glutamine gamma-glutamyltransferase E, Antibody Fab fragment heavy chain IGHV2-5, Antibody Fab fragment light chain IGKV4-1, ... (6 entities in total) |
| Functional Keywords | transglutaminase, autoantibody, dermatitis herpetiformis, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 199101.40 |
| Authors | Heggelund, J.E.,Sollid, L.M. (deposition date: 2024-01-09, release date: 2025-03-12, Last modification date: 2025-03-19) |
| Primary citation | Iversen, R.,Heggelund, J.E.,Das, S.,Hoydahl, L.S.,Sollid, L.M. Enzyme-activating B-cell receptors boost antigen presentation to pathogenic T cells in gluten-sensitive autoimmunity. Nat Commun, 16:2387-2387, 2025 Cited by PubMed Abstract: Autoantibodies against the enzyme transglutaminase 3 (TG3) are characteristic to the gluten-sensitive skin disorder dermatitis herpetiformis (DH), which is an extraintestinal manifestation of celiac disease. We here demonstrate that TG3-specific B cells can activate gluten-specific CD4 T cells through B-cell receptor (BCR)-mediated internalization of TG3-gluten enzyme-substrate complexes. Stereotypic anti-TG3 antibodies using IGHV2-5/IGKV4-1 gene segments enhance the catalytic activity of TG3, and this effect translates into increased gluten presentation to T cells when such antibodies are expressed as BCRs. The crystal structure of TG3 bound to an IGHV2-5/IGKV4-1 Fab shows that antibody binding to a β-sheet in the catalytic core domain causes the enzyme to adopt the active conformation. This mechanism explains the production of stereotypic anti-TG3 autoantibodies in DH and highlights a role for TG3-specific B cells as antigen-presenting cells for gluten-specific T cells. Similar boosting effects of autoreactive BCRs could be relevant for other autoimmune diseases, including rheumatoid arthritis. PubMed: 40064932DOI: 10.1038/s41467-025-57564-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.803 Å) |
Structure validation
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