Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.

Bhattacharyya, M, Stratton, MM, Going, CC, McSpadden, ED, Huang, Y, Susa, AC, Elleman, A, Cao, YM, Pappireddi, N, Burkhardt, P, Gee, CL, Barros, T, Schulman, H, Williams, ER and Kuriyan, J 2016 Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.. eLife, 5. https://doi.org/10.7554/eLife.13405

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Abstract/Summary

Activation triggers the exchange of subunits in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones.

Item Type: Publication - Article
Divisions: Marine Biological Association of the UK > Marine Microbiome
Depositing User: Dr Pawel Burkhardt
Date made live: 17 Aug 2016 11:03
Last Modified: 09 Feb 2024 17:05
URI: https://plymsea.ac.uk/id/eprint/7118

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