6FCM

Crystal structure of human PCNA

6FCM の概要

• エントリーDOI: 10.2210/pdb6fcm/pdb
• 関連するPDBエントリー: 1AXC
• 分子名称: Proliferating cell nuclear antigen (2 entities in total)
• 機能のキーワード: proliferating cell nuclear antigen, nuclear protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 93294.87

構造登録者

Housset, D.,Frachet, P. (登録日: 2017-12-20, 公開日: 2019-01-30, 最終更新日: 2024-10-16)

主引用文献

Ohayon, D.,De Chiara, A.,Dang, P.M.,Thieblemont, N.,Chatfield, S.,Marzaioli, V.,Burgener, S.S.,Mocek, J.,Candalh, C.,Pintard, C.,Tacnet-Delorme, P.,Renault, G.,Lagoutte, I.,Favier, M.,Walker, F.,Hurtado-Nedelec, M.,Desplancq, D.,Weiss, E.,Benarafa, C.,Housset, D.,Marie, J.C.,Frachet, P.,El-Benna, J.,Witko-Sarsat, V.
Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils.
J.Exp.Med., 216:2669-2687, 2019

PubMed Abstract: Neutrophils produce high levels of reactive oxygen species (ROS) by NADPH oxidase that are crucial for host defense but can lead to tissue injury when produced in excess. We previously described that proliferating cell nuclear antigen (PCNA), a nuclear scaffolding protein pivotal in DNA synthesis, controls neutrophil survival through its cytosolic association with procaspases. We herein showed that PCNA associated with p47phox, a key subunit of NADPH oxidase, and that this association regulated ROS production. Surface plasmon resonance and crystallography techniques demonstrated that the interdomain-connecting loop of PCNA interacted directly with the phox homology PX) domain of the p47phox. PCNA inhibition by competing peptides or by T2AA, a small-molecule PCNA inhibitor, decreased NADPH oxidase activation in vitro. Furthermore, T2AA provided a therapeutic benefit in mice during trinitro-benzene-sulfonic acid (TNBS)-induced colitis by decreasing oxidative stress, accelerating mucosal repair, and promoting the resolution of inflammation. Our data suggest that targeting PCNA in inflammatory neutrophils holds promise as a multifaceted antiinflammatory strategy.

PubMed: 31492810
DOI: 10.1084/jem.20180371

実験手法

X-RAY DIFFRACTION (2.8 Å)