Abstract
Protein kinase CK2 consists of two catalytic subunits (CK2α) and two regulatory subunits (CK2β). Here, we report the crystal structures of rat CK2α mutant (rCK2α-ΔC, 1–335) and CK2β (rCK2β). The overall topology of rCK2α-ΔC and rCK2β are very similar to the human enzyme, although large structural differences could be observed in the N-terminal domain of rCK2α-ΔC. Our reported structure of rCK2α-ΔC is in the close conformation state while the counterpart hCK2α is in the open conformation state, indicating the conformation of CK2α molecule has high plasticity. The structure of rCK2β represents the conformation of free CK2β. Upon CK2α binding, the C-terminal region undergoes a drastic conformational change. The major region of interaction within the interface of CK2α/CK2β may serve as a bridge to transmit the conformational change and thus regulate the activity of CK2α.
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Yde C W, Ermakova I, Issinger O G, et al. Inclining the purine base binding plane in protein kinase CK2 by exchanging the flanking side-chains generates a preference for ATP as a cosubstrate. J Mol Biol, 2005, 347: 399–414
Pinna L A. Protein kinase CK2: A challenge to canons. J Cell Sci, 2002, 115: 3873–3878
Meggio F, Pinna L A. One-thousand-and-one substrates of protein kinase CK2? FASEB J, 2003, 17: 349–368
Wang G, Ahmad K A, Ahmed K. Role of protein kinase CK2 in the regulation of tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis in prostate cancer cells. Cancer Res, 2006, 66: 2242–2249
Seldin D C. New models of lymphoma in transgenic mice. Curr Opin Immunol, 1995, 7: 665–673
Harada S, Haneda E, Maekawa T, et al. Casein kinase II (CK-II)-mediated stimulation of HIV-1 reverse transcriptase activity and characterization of selective inhibitors in vitro. Biol Pharm Bull, 1999, 22: 1122–1126
Niefind K, Guerra B, Ermakowa I, et al. Crystal structure of human protein kinase CK2: Insights into basic properties of the CK2 holoenzyme. EMBO J, 2001, 20: 5320–5331
Benitez M J, Cochet C, Jimenez J S. A surface plasmon resonance study of the interactions between the component subunits of protein kinase CK2 and two protein substrates, casein and calmodulin. Mol Cell Biochem, 2001, 227: 31–36
Benitez M J, Mier G, Brione F, et al. Binding of polylysine to protein kinase CK2, measured by Surface Plasmon Resonance. Mol Cell Biochem, 1999, 191: 29–33
Guerra B, Gotz C, Wagner P, et al. The carboxy terminus of p53 mimics the polylysine effect of protein kinase CK2-catalyzed MDM2 phosphorylation. Oncogene, 1997, 14: 2683–2688
Niefind K, Yde C W, Ermakova I, et al. Evolved to be active: Sulfate ions define substrate recognition sites of CK2a and emphasise its exceptional role within the CMGC family of eukaryotic protein kinases. J Mol Biol, 2007, 370: 427–438
Chantalat L, Leroy D, Filhol O, et al. Crystal structure of the human protein kinase CK2 regulatory subunit reveals its zinc finger-mediated dimerization. EMBO J, 1999, 18: 2930–2940
Raaf J, Klopffleisch K, Issinger O G et al. The catalytic subunit of human protein kinase CK2 structurally deviates from its maize homologue in complex with the nucleotide competitive inhibitor emodin. J Mol Biol, 2008, 377: 1–8
Poole A, Poore T, Bandhakavi S, et al. A global view of CK2 function and regulation. Mol Cell Biochem, 2005, 274: 163–170
Battistutta R, Mazzorana M, Cendron L, et al. The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules. Chembiochem, 2007, 8: 1804–1809
Bolanos-Garcia V M, Fernandez-Recio J, Allende J E, et al. Identifying interaction motifs in CK2beta-a ubiquitous kinase regulatory subunit. Trends Biochem Sci, 2006, 31: 654–661
Bertrand L, Sayed M F, Pei X Y, et al. Structure of the regulatory subunit of CK2 in the presence of a p21WAF1 peptide demonstrates flexibility of the acidic loop. Acta Crystallogr D, 2004, 60: 1698–1704
Hagemann C, Kalmes A, Wixler V, et al. The regulatory subunit of protein kinase CK2 is a specific A-Raf activator. FEBS Lett, 1997, 403: 200–202
Lieberman S L, Ruderman J V. CK2 beta, which inhibits Mos function, binds to a discrete domain in the N-terminus of Mos. Dev Biol, 2004, 268: 271–279
Otwinowski Z, Minor W. Processing of x-ray diffraction data collected in oscillation mode. Methods Enzymol, 1997, 276: 307–326
McCoy A J. Solving structures of protein complexes by molecular replacement with Phaser. Acta crystallogr D, 2007, 63: 32–41
Emsley P, Cowtan K. Coot: Model-building tools for molecular graphics. Acta Crystallogr D, 2004, 60: 2126–2132
Brunger A T, Adams P D, Clore G M, et al. Crystallography & NMR system: A new software suite for macro-molecular structure determination. Acta Crystallogr D, 1998, 54: 905–921
Laskowski R A, Macarthur M W, Moss D S, et al. PROCHECK-a program to check the stereochemical quality of protein structures. J Appl Crystallogr, 1993, 26: 283–291
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Supported by Tianjin Basic Research Program (Grant No. 07JCYBJC15600), National Natural Science Foundation of China (Grant No. 30770428), National Key Basic Research and Development Program of China (Grant Nos. 2007CB914301, 2006CB910200), National High-Technology Research and Development Program of China (Grant No. 2006AA02A319) and National Institute of Health (Grant No. MH07752)
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Zhou, W., Qin, X., Yan, X. et al. Crystal structures of catalytic and regulatory subunits of rat protein kinase CK2. Chin. Sci. Bull. 54, 220–226 (2009). https://doi.org/10.1007/s11434-008-0580-2
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DOI: https://doi.org/10.1007/s11434-008-0580-2