CK2 Tetrameric Assembly
In vivo, human CK2 is found mainly, although not exclusively, in a tetrameric assembly, composed of two catalytic a- (or a') and two regulatory b-sub-units. Evidence has accumulating that these subunits can exist in vivo also in isolated forms, with specific functions (Pinna and Meggio 1997). While the catalytic subunit, when isolated, is found in a monomeric state, the regulatory subunits have a strong tendency to form dimers, due to the presence of a zinc-finger motif (Chantalat et al. 1999). This dimeric state is spontaneously formed in solution and is thought to be responsible for the recruitment of the two catalytic subunits in order to assemble the final tetramer (Graham and Litchfield 2000).
The three-dimensional structure of the human holoenzyme, carrying a-subunits lacking of the C-terminal tail, was determined at 3.1 A resolution
(Niefind et al. 2001). Even if the quality of the final model at this resolution is limited, nevertheless it clearly indicates that the catalytic subunit is poorly affected by the presence of the regulatory one. In other words, the inclusion in the tetramer does not significantly modify the structure of the isolated human catalytic subunit. The overall structure of the holoenzyme shows a "butterfly" shape, where the regulatory dimer, whose structure is very similar to that in the isolated form, binds two a-subunits that do not interact with each other. The surfaces of interaction between the subunits are not extensive, and this is somewhat unexpected due to the remarkable resistance to the action of denaturing agents showed by the holoenzyme. The interpretation of the large amount of biochemical and functional data accumulated in the years is not always straightforward in terms of the structural properties unveiled by the three-dimensional structure of the holoenzyme. This analysis is currently underway and is subject of debate in the field.
Was this article helpful?