8RMY

Transglutaminase 3 in complex with inhibitor Z-don and DH patient-derived Fab DH63-A02

8RMY の概要

• エントリーDOI: 10.2210/pdb8rmy/pdb
• 関連するPDBエントリー: 8RMX
• 分子名称: Antibody Fab fragment light chain IGKV4-1, Protein-glutamine gamma-glutamyltransferase E, Antibody Fab fragment heavy chain IGHV2-5, ... (9 entities in total)
• 機能のキーワード: transglutaminase, tg3, tgm3, inhibitor, antibody, calcium, transferase
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 200350.65

構造登録者

Heggelund, J.E.,Sollid, L.M. (登録日: 2024-01-09, 公開日: 2025-03-12, 最終更新日: 2025-03-19)

主引用文献

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

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: 40064932
DOI: 10.1038/s41467-025-57564-5

実験手法

X-RAY DIFFRACTION (2.9 Å)