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

A. V. Sokolov1,2,3,4#, L. A. Dadinova5#, M. V. Petoukhov5,6,7,8, G. Bourenkov6, K. M. Dubova5, S. V. Amarantov5, V. V. Volkov5, V. A. Kostevich1,2, N. P. Gorbunov1, N. A. Grudinina1, V. B. Vasilyev1,3, and V. R. Samygina5,9,a*

1Institute of Experimental Medicine, 197376 St. Petersburg, Russia

2Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia

3St. Petersburg State University, 199000 St. Petersburg, Russia

4Center of Preclinical Translational Research, Almazov National Medical Research Center, 197371 St. Petersburg, Russia

5Shubnikov Institute of Crystallography, FSRC “Crystallography and Photonics”, Russian Academy of Sciences, 119333 Moscow, Russia

6European Molecular Biology Laboratory (EMBL), 22607 Hamburg, Germany

7Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 119071 Moscow, Russia

8Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia

9National Research Center “Kurchatov Institute”, 123182 Moscow, Russia

# These authors contributed equally to this work.

* To whom correspondence should be addressed.

Received November 1, 2017; Revision received February 2, 2018
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.
KEY WORDS: X-ray analysis, small-angle X-ray scattering, protein–protein interactions, ceruloplasmin, macrophage migration inhibitory factor

DOI: 10.1134/S000629791806007X