3ZUI

OMCI in complex with palmitoleic acid

3ZUI の概要

• エントリーDOI: 10.2210/pdb3zui/pdb
• 関連するPDBエントリー: 2CM4 2CM9 3ZUO
• 分子名称: COMPLEMENT INHIBITOR, PALMITOLEIC ACID (3 entities in total)
• 機能のキーワード: immune system, soft tick, argasid tick, c5, lipocalin complement
• 由来する生物種: ORNITHODOROS MOUBATA
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17058.99

構造登録者

Roversi, P.,Maillet, I.,Togbe, D.,Couillin, I.,Quesniaux, V.F.J.,Teixeira, M.,Ahmat, N.,Lissina, O.,Boland, W.,Ploss, K.,Caesar, J.J.E.,Leonhartsberger, S.,Ryffel, B.,Lea, S.M.,Nunn, M.A. (登録日: 2011-07-19, 公開日: 2012-08-01, 最終更新日: 2024-10-23)

主引用文献

Roversi, P.,Ryffel, B.,Togbe, D.,Maillet, I.,Teixeira, M.,Ahmat, N.,Paesen, G.C.,Lissina, O.,Boland, W.,Ploss, K.,Caesar, J.J.,Leonhartsberger, S.,Lea, S.M.,Nunn, M.A.
Bifunctional Lipocalin Ameliorates Murine Immune Complex-Induced Acute Lung Injury.
J.Biol.Chem., 288:18789-, 2013

PubMed Abstract: Molecules that simultaneously inhibit independent or co-dependent proinflammatory pathways may have advantages over conventional monotherapeutics. OmCI is a bifunctional protein derived from blood-feeding ticks that specifically prevents complement (C)-mediated C5 activation and also sequesters leukotriene B4 (LTB4) within an internal binding pocket. Here, we examined the effect of LTB4 binding on OmCI structure and function and investigated the relative importance of C-mediated C5 activation and LTB4 in a mouse model of immune complex-induced acute lung injury (IC-ALI). We describe two crystal structures of bacterially expressed OmCI: one binding a C16 fatty acid and the other binding LTB4 (C20). We show that the C5 and LTB4 binding activities of the molecule are independent of each other and that OmCI is a potent inhibitor of experimental IC-ALI, equally dependent on both C5 inhibition and LTB4 binding for full activity. The data highlight the importance of LTB4 in IC-ALI and activation of C5 by the complement pathway C5 convertase rather than by non-C proteases. The findings suggest that dual inhibition of C5 and LTB4 may be useful for treatment of human immune complex-dependent diseases.

PubMed: 23625922
DOI: 10.1074/JBC.M112.420331

実験手法

X-RAY DIFFRACTION (1.71 Å)