Primary and secondary interactions between CK2α and CK2β lead to ring-like structures in the crystals of the CK2 holoenzyme

Protein kinase CK2 predominantly exists as a heterotetrameric holoenyzme consisting of two catalytic subunits (CK2 alpha) and two non-catalytic subunits (CK2 beta). Early investigations which we review here had revealed the presence of two types of contacts between CK2 alpha and CK2 beta: a primary interaction responsible for the stability of the CK2 holoenzyme and stimulatory for the catalytic activity, and a secondary interaction which is inhibitory and in which the acidic loop of CK2 beta associates with the basic stretch and the (p+1)-loop of CK2 alpha. At the end of the last decade both types of interactions were assumed to occur within the same tetrameric complex. The CK2 holoenyzme structure, however, suggested that the secondary interactions must happen between different CK2 tetramers. Such a behaviour should lead to higher-ordered aggregates consistent with several previous reports about a distinct aggregation propensity of CK2. We demonstrate here that in the CK2 holoenzyme crystals contacts between different CK2 tetramers exists which provide structural details of the secondary CK2 alpha/CK2 beta interactions. These mainly ionic interactions lead to trimeric rings of CK2 holoenzymes in the crystal. In these rings each CK2 tetramer possesses one CK2 alpha subunit open for substrate binding and another one whose active site is blocked by a secondary contact with CK2 beta from a neighbouring tetramer. This observation fits to previous findings that salt-sensitive ring-like aggregates of CK2 holoenzymes can exist which possess significant catalytic activity. Furthermore it suggests that earlier ideas about a regulatory role of the enzyme's aggregation propensity may be worth to be revitalised.