Conserved and divergent features of neuronal CaMKII holoenzyme structure, function, and high-order assembly
| Autor: | Olivia R. Buonarati, Steve L. Reichow, Adam P. Miller, K. U. Bayer, Steven J. Coultrap |
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| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Male Neurons Calmodulin biology Chemistry Protein Conformation Structure function Hippocampus In vitro Single Molecule Imaging General Biochemistry Genetics and Molecular Biology Mice Inbred C57BL Mice Holoenzymes Ca2+/calmodulin-dependent protein kinase Biophysics biology.protein Animals Female High order Phosphorylation Beta (finance) Calcium-Calmodulin-Dependent Protein Kinase Type 2 |
| Zdroj: | Cell Reports. 37:110168 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.110168 |
| Popis: | SUMMARYNeuronal 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, bothin vitroand in neurons. |
| Databáze: | OpenAIRE |
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