8OXV

Transglutaminase 3 zymogen in complex with DH patient-derived Fab DH63-B02

8OXV の概要

• エントリーDOI: 10.2210/pdb8oxv/pdb
• 分子名称: Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain, Antibody Fab fragment Heavy chain, Antibody Fab fragment light chain, ... (7 entities in total)
• 機能のキーワード: transglutaminase, tgm3, tg3, transglutaminase 3, enzyme, zymogen, antibody, dermatitis herpetiformis, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 124310.81

構造登録者

Heggelund, J.E.,Sollid, L.M. (登録日: 2023-05-02, 公開日: 2023-10-18, 最終更新日: 2024-11-13)

主引用文献

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

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: 37798283
DOI: 10.1038/s41467-023-42004-z

実験手法

X-RAY DIFFRACTION (1.8 Å)