Ceruloplasmin: Macromolecular Assemblies with Iron-Containing Acute Phase Proteins
| Autor: | Tuma, Roman, Sokolov, Alexey V., Bourenkov, Gleb, Petoukhov, Maxim, Pulina, Maria O., Zakharova, Elena T., Vasilyev, Vadim B., Bartunik, Hans, Svergun, Dmitri, Samygina, Valeriya |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Macromolecular Assemblies
Proteomics Models Molecular Protein Conformation Glycobiology lcsh:Medicine Plasma protein binding Crystallography X-Ray Ferroxidase activity Biochemistry chemistry.chemical_compound Protein structure Biomacromolecule-Ligand Interactions lcsh:Science Condensed-Matter Physics Ternary complex Heme 0303 health sciences Immune System Proteins Crystallography Multidisciplinary biology Chemistry Physics 030302 biochemistry & molecular biology Ceruloplasmin Enzymes Solutions Myeloperoxidase ddc:500 Research Article Protein Binding Protein Structure Iron Biophysics Protein–protein interaction Enzyme Regulation 03 medical and health sciences Defense Proteins Humans Protein Interaction Domains and Motifs Protein Interactions Biology Glycoproteins Peroxidase 030304 developmental biology Plasma Proteins Chemical Physics lcsh:R Proteins Lactoferrin Multiprotein Complexes biology.protein lcsh:Q Acute-Phase Proteins |
| Zdroj: | PLoS one 8(7), e67145 (2013). doi:10.1371/journal.pone.0067145 PLoS ONE, Vol 8, Iss 7, p e67145 (2013) PLoS ONE |
| DOI: | 10.1371/journal.pone.0067145 |
| Popis: | 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 A 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 1ratio1 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. |
| Databáze: | OpenAIRE |
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