Conserved and divergent features of neuronal CaMKII holoenzyme structure, function, and high-order assembly

Here, we provide a comparative analysis of these signaling devices, using single particle EM in combination with biochemical and live-cell imaging studies. In the basal state, both isoforms assembled mainly as 12-mers (but also 14-mers, and even 16-mers for the β-isoform).

CaMKIIα and β-isoforms adopted an ensemble of extended activatable states (with average radius of 12.6 versus 16.8 nm, respectively), characterized by multiple transient intra- and inter-holoenzyme interactions associated with distinct functional properties. The extended state of CaMKIIβ allowed EM analysis to directly resolve intra-holoenzyme kinase-domain dimers that could enable the cooperative activation mechanism by calmodulin, which was found for both isoforms.