9HUI

CryoEM structure of human peptidylarginine deiminase type 4 (PAD4) in complex with heparin oligomer (20 subunits).

9HUI の概要

• エントリーDOI: 10.2210/pdb9hui/pdb
• EMDBエントリー: 52414
• 分子名称: Protein-arginine deiminase type-4 (1 entity in total)
• 機能のキーワード: pad4, citrullination, calcium, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 151745.81

構造登録者

Bereta, G.,Bielecka, E.,Biela, A.,Wilk, P.,Wator-Wilk, E.,Grudnik, P.,Kantyka, T. (登録日: 2024-12-23, 公開日: 2025-10-22, 最終更新日: 2025-11-12)

主引用文献

Bereta, G.P.,Bielecka, E.,Marzec, K.,Pijanowski, L.,Biela, A.P.,Wilk, P.,Kaminska, M.,Nowak, J.,Wator-Wilk, E.,Grudnik, P.,Kowalczyk, D.,Koziel, J.,Mydel, P.,Poreba, M.,Kantyka, T.
Glycosaminoglycans activate peptidylarginine deiminase 4 by enhancing calcium affinity.
Proc.Natl.Acad.Sci.USA, 122:e2508369122-e2508369122, 2025

PubMed Abstract: Rheumatoid arthritis is a chronic inflammatory disease driven by abnormal protein modifications. These include citrullination of arginine residues by the calcium-activated enzyme peptidylarginine deiminase 4 (PAD4). However, calcium in body fluids may not fully activate PAD4, suggesting the potential involvement of other activators. In this study, we investigated the ability of glycosaminoglycans (a class of negatively charged polysaccharides) to modulate PAD4 activity. We found that model glycosaminoglycans bind to the enzyme with a nanomolar affinity, increase its calcium sensitivity, and require enzyme dimerization for activation. These effects depend on the size and negative charge of the glycosaminoglycan, and its various natural forms activate PAD4. Thus, our findings elucidate a mechanism by which common physiological compounds modulate PAD4 activity, potentially contributing to disease etiology.

PubMed: 41166417
DOI: 10.1073/pnas.2508369122

実験手法

ELECTRON MICROSCOPY (3.73 Å)