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

doi:10.1134/S000629791806007X

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

Biochemistry (Mosc). 2018 Jun;83(6):701-707. doi: 10.1134/S000629791806007X.

Authors

A V Sokolov^#^{1

2

3

4}, L A Dadinova^#⁵, M V Petoukhov^{5

6

7

8}, G Bourenkov⁶, K M Dubova⁵, S V Amarantov⁵, V V Volkov⁵, V A Kostevich^{1

2}, N P Gorbunov¹, N A Grudinina¹, V B Vasilyev^{1

3}, V R Samygina^{9

10}

Affiliations

¹ Institute of Experimental Medicine, St. Petersburg, 197376, Russia.
² Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, 119435, Russia.
³ St. Petersburg State University, St. Petersburg, 199000, Russia.
⁴ Center of Preclinical Translational Research, Almazov National Medical Research Center, St. Petersburg, 197371, Russia.
⁵ Shubnikov Institute of Crystallography, FSRC "Crystallography and Photonics", Russian Academy of Sciences, Moscow, 119333, Russia.
⁶ European Molecular Biology Laboratory (EMBL), Hamburg, 22607, Germany.
⁷ Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, 119071, Russia.
⁸ Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 119991, Russia.
⁹ Shubnikov Institute of Crystallography, FSRC "Crystallography and Photonics", Russian Academy of Sciences, Moscow, 119333, Russia. lera@crys.ras.ru.
¹⁰ National Research Center "Kurchatov Institute", Moscow, 123182, Russia.

^# Contributed equally.

PMID: 30195326
DOI: 10.1134/S000629791806007X

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.

MeSH terms

Ceruloplasmin / chemistry
Ceruloplasmin / metabolism*
Chromatography, Gel
Copper / chemistry
Copper / metabolism
Crystallography, X-Ray
Fluorescein-5-isothiocyanate / chemistry
Humans
Isothiocyanates / chemistry
Macrophage Migration-Inhibitory Factors / chemistry
Macrophage Migration-Inhibitory Factors / genetics
Macrophage Migration-Inhibitory Factors / metabolism*
Protein Binding
Protein Structure, Quaternary
Recombinant Proteins / biosynthesis
Recombinant Proteins / chemistry
Recombinant Proteins / isolation & purification
Scattering, Small Angle
X-Ray Diffraction

Substances

Isothiocyanates
Macrophage Migration-Inhibitory Factors
Recombinant Proteins
phenylisothiocyanate
Copper
Ceruloplasmin
Fluorescein-5-isothiocyanate