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


Autoria(s): 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; Kuriyan, J
Data(s)

07/03/2016

Resumo

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.

Formato

text

text

Identificador

http://plymsea.ac.uk/7118/1/elife13405-figures.pdf

http://plymsea.ac.uk/7118/2/e13405-download.pdf

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; Kuriyan, J. 2016 Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.. eLife, 5. /10.7554/eLife.13405 <http://doi.org//10.7554/eLife.13405>

Idioma(s)

en

en

Relação

http://plymsea.ac.uk/7118/

http://dx.doi.org/10.7554/eLife.13405

Direitos

cc_by

cc_by

Tipo

Publication - Article

PeerReviewed