2PND

Structure or murine CRIg

2PND の概要

• エントリーDOI: 10.2210/pdb2pnd/pdb
• 関連するPDBエントリー: 2ICC 2ICE 2ICF
• 分子名称: V-set and immunoglobulin domain containing 4 (2 entities in total)
• 機能のキーワード: complement receptor, ig-like domain, immune system
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13761.72

構造登録者

Wiesmann, C. (登録日: 2007-04-24, 公開日: 2007-05-01, 最終更新日: 2023-08-30)

主引用文献

Katschke, K.J.,Helmy, K.Y.,Steffek, M.,Xi, H.,Yin, J.,Lee, W.P.,Gribling, P.,Barck, K.H.,Carano, R.A.,Taylor, R.E.,Rangell, L.,Diehl, L.,Hass, P.E.,Wiesmann, C.,van Lookerenb Campagne, M.
A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis.
J.Exp.Med., 204:1319-1325, 2007

PubMed Abstract: Complement is an important component of the innate and adaptive immune response, yet complement split products generated through activation of each of the three complement pathways (classical, alternative, and lectin) can cause inflammation and tissue destruction. Previous studies have shown that complement activation through the alternative, but not classical, pathway is required to initiate antibody-induced arthritis in mice, but it is unclear if the alternative pathway (AP) plays a role in established disease. Previously, we have shown that human complement receptor of the immunoglobulin superfamily (CRIg) is a selective inhibitor of the AP of complement. Here, we present the crystal structure of murine CRIg and, using mutants, provide evidence that the structural requirements for inhibition of the AP are conserved in human and mouse. A soluble form of CRIg reversed inflammation and bone loss in two experimental models of arthritis by inhibiting the AP of complement in the joint. Our data indicate that the AP of complement is not only required for disease induction, but also disease progression. The extracellular domain of CRIg thus provides a novel tool to study the effects of inhibiting the AP of complement in established disease and constitutes a promising therapeutic with selectivity for a single complement pathway.

PubMed: 17548523
DOI: 10.1084/jem.20070432

実験手法

X-RAY DIFFRACTION (1 Å)