4EJX

Structure of ceruloplasmin-myeloperoxidase complex

4EJX の概要

• エントリーDOI: 10.2210/pdb4ejx/pdb
• 関連するPDBエントリー: 4ENZ
• 分子名称: Ceruloplasmin, Myeloperoxidase light chain, Myeloperoxidase heavy chain, ... (7 entities in total)
• 機能のキーワード: cupredoxin domains, glycoproteins, protein-protein interaction, oxidoreductase
• 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: 191073.37

構造登録者

Samygina, V.R.,Sokolov, A.V.,Bourenkov, G.,Vasilyev, V.B.,Bartunik, H. (登録日: 2012-04-07, 公開日: 2013-04-10, 最終更新日: 2024-11-06)

主引用文献

Samygina, V.R.,Sokolov, A.V.,Bourenkov, G.,Petoukhov, M.V.,Pulina, M.O.,Zakharova, E.T.,Vasilyev, V.B.,Bartunik, H.,Svergun, D.I.
Ceruloplasmin: macromolecular assemblies with iron-containing acute phase proteins.
Plos One, 8:e67145-e67145, 2013

PubMed Abstract: Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein-protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1:1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe(3+) into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage.

PubMed: 23843990
DOI: 10.1371/journal.pone.0067145

実験手法

X-RAY DIFFRACTION (4.69 Å)