Structural Study of the Complex Formed by Ceruloplasmin and Macrophage Migration Inhibitory Factor.

A V Sokolov, L A Dadinova, M V Petoukhov, G Bourenkov, K M Dubova, S V Amarantov, V V Volkov, V A Kostevich, N P Gorbunov, N A Grudinina, V B Vasilyev, V R Samygina

Journal: Biochemistry. Biokhimiia 2018;83(6):701-707

PMID: 30195326

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Abstract

Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine. Inhibitors of tautomerase activity of MIF are perspective antiinflammatory compounds. Ceruloplasmin, the copper-containing ferroxidase of blood plasma, is a noncompetitive inhibitor of tautomerase activity of MIF in the reaction with p-hydroxyphenylpyruvate. Small-angle X-ray scattering established a model of the complex formed by MIF and ceruloplasmin. Crystallographic analysis of MIF with a modified active site supports the model. The stoichiometry of 3 CP/MIF trimer complex was established using gel filtration. Conformity of novel data concerning the interaction regions in the studied proteins with previous biochemical data is discussed.

Address: Institute of Experimental Medicine, St. Petersburg, 197376, Russia.; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, 119435, Russia.; St. Petersburg State University, St. Petersburg, 199000, Russia.; Center of Preclinical Translational Research, Almazov National Medical Research Center, St. Petersburg, 197371, Russia.; Shubnikov Institute of Crystallography, FSRC "Crystallography and Photonics", Russian Academy of Sciences, Moscow, 119333, Russia.; Shubnikov Institute of Crystallography, FSRC "Crystallography and Photonics", Russian Academy of Sciences, Moscow, 119333, Russia.; European Molecular Biology Laboratory (EMBL), Hamburg, 22607, Germany.; Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, 119071, Russia.; Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 119991, Russia.; European Molecular Biology Laboratory (EMBL), Hamburg, 22607, Germany.; Institute of Experimental Medicine, St. Petersburg, 197376, Russia.; Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, 119435, Russia.; Institute of Experimental Medicine, St. Petersburg, 197376, Russia.; Institute of Experimental Medicine, St. Petersburg, 197376, Russia.; St. Petersburg State University, St. Petersburg, 199000, Russia.; Shubnikov Institute of Crystallography, FSRC "Crystallography and Photonics", Russian Academy of Sciences, Moscow, 119333, Russia. [email protected].; National Research Center "Kurchatov Institute", Moscow, 123182, Russia.

DOI: 10.1134/S000629791806007X

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MeSH Terms: Ceruloplasmin, Chromatography, Gel, Copper, Crystallography, X-Ray, Fluorescein-5-isothiocyanate, Humans, Isothiocyanates, Macrophage Migration-Inhibitory Factors, Protein Binding, Protein Structure, Quaternary, Recombinant Proteins, Scattering, Small Angle, X-Ray Diffraction