Calcium sensing by CaMKII

Our lab has also provided the first structural descriptions of the calcium/calmodulin-dependent protein kinase II (CaMKII). Interest in CaMKII arises because of its ability to respond not just to the amplitude but also the frequency of calcium spikes, which makes it one of the critical molecular components underlying long term potentiation in neurons. The action of CaMK-II is balanced by that of the protein phosphatase known as PP1, the structure of which our group was also the first to determine (Goldberg et al., Nature 1995).

CaMKII is unique among protein kinases for its dodecameric assembly and we recently determined the first crystal structure of an intact fully auto-inhibited human CaMKII holoenzyme assembly (Chao et al., Cell 2011). The structure shows a tight integration of all 12 kinase domains around the central hub and, combined with SAXS measurements, explains how access to calmodulin is controlled and how nature tunes the spike frequency threshold for the activation of different isoforms.