2026-10-14T10:08:21Z https://data.mendeley.com/oai

oai:data.mendeley.com/35gf4sjxmb.1 2021-10-25T20:17:59Z

Buonarati, Olivia Conserved and divergent features of neuronal CaMKII holoenzyme structure, function, and high-order assembly Mendeley Data Neuronal CaMKII holoenzymes (α- and β-isoforms) enable molecular signal computation underlying learning and memory, but also mediate excitotoxic neuronal death. 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. Surprisingly, high-order CaMKII clustering mediated by inter-holoenzyme kinase-domain dimerization was reduced for the β isoform for both basal and excitotoxicity-induced clusters, both in vitro and in neurons. Molecular Neuroscience Clustering Protein Structure Kinase Miller, Adam Coultrap, Steven Bayer, K. Ulrich Reichow, Steve Dataset doi:10.17632/35gf4sjxmb.1 oai:data.mendeley.com/35gf4sjxmb.1 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/35gf4sjxmb 2021-10-25T20:17:59Z