Quaternary Structure of Casein Kinase 2

• Published in: The Journal of biological chemistry Vol. 270; no. 14; pp. 8345 - 8352
• Main Authors: Valero, Emmanuelle, De Bonis, Salvatore, Filhol, Odile, Wade, Richard H., Langowski, Joerg, Chambaz, Edmond M., Cochet, Claude
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 07.04.1995; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.14.8345

The structure-activity relationship of casein kinase 2 (CK2) was examined with regard to its previously reported property to self-aggregate in vitro. Sedimentation velocity and electron microscopy studies showed that the purified kinase exhibited four major, different oligomeric forms in aqueous solution. This self-polymerization was a reproducible and fully reversible process, highly dependent upon the ionic strength of the medium, suggesting that electrostatic interactions are mostly involved. At high salt concentrations (e.g. 0.5 M NaCl), CK2 appears as spherical moieties with a 18.7 ± 1.6 nm average diameter, roughly corresponding to the α2β2 protomer, as deduced by measurements of the Stokes radius and by light scattering studies. At lower ionic strength (e.g. 0.2 M NaCl), the protomers associate to form ring-like structures with a diameter (averaging 36.6 ± 2.1 nm) and Stokes radius indicating that they are most likely made of four circularly associated α2β2 protomers. At 0.1 M NaCl, two additional polymeric structures were visualized: thin filaments (16.4 ± 1.4 nm average), as long as 1 to 5 μm, and thick and shorter filaments (28.5 ± 1.6 nm average). Examination of the molecular organization of CK2 under different catalytic conditions revealed that the ring-like structure is the favored conformation adopted by the enzyme in the presence of saturating concentrations of substrates and cofactors. During catalysis, well-known cofactors like MgCl2 or spermine are the main factors governing the stabilization of the active ring-like structure. On the other hand, inhibitory high salt concentrations promote the dissociation of the active ring-like structure into protomers. Such observations suggest a strong correlation between the ring-like conformation of the enzyme and optimal specific activity. Thus, CK2 may be considered as an associating-dissociating enzyme, and this remarkable property supports the hypothesis of a cooperative and allosteric regulation of the kinase in response to appropriate regulatory ligands possibly taking place in intact cells.