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University of Massachusetts Amherst
Biochemistry & Molecular Biology Department Faculty Publication Series
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Full-Text Articles in Molecular Biology
Activation-Triggered Subunit Exchange Between Camkii Holoenzymes Facilitates The Spread Of Kinase Activity, Margaret M. Stratton, I H. Lee, M Bhattacharyya, S M. Christensen, L H. Chao, H Schulman, J T. Groves, J Kuriyan
Activation-Triggered Subunit Exchange Between Camkii Holoenzymes Facilitates The Spread Of Kinase Activity, Margaret M. Stratton, I H. Lee, M Bhattacharyya, S M. Christensen, L H. Chao, H Schulman, J T. Groves, J Kuriyan
Biochemistry & Molecular Biology Department Faculty Publication Series
The activation of the dodecameric Ca2+/calmodulin dependent kinase II (CaMKII) holoenzyme is critical for memory formation. We now report that CaMKII has a remarkable property, which is that activation of the holoenzyme triggers the exchange of subunits between holoenzymes, including unactivated ones, enabling the calcium-independent phosphorylation of new subunits. We show, using a single-molecule TIRF microscopy technique, that the exchange process is triggered by the activation of CaMKII, and that exchange is modulated by phosphorylation of two residues in the calmodulin-binding segment, Thr 305 and Thr 306. Based on these results, and on the analysis of molecular dynamics simulations, we …