Structural highlights
Evolutionary Conservation
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Publication Abstract from PubMed
The dodecameric holoenzyme of calcium-calmodulin-dependent protein kinase II (CaMKII) responds to high-frequency Ca(2+) pulses to become Ca(2+) independent. A simple coincidence-detector model for Ca(2+)-frequency dependency assumes noncooperative activation of kinase domains. We show that activation of CaMKII by Ca(2+)-calmodulin is cooperative, with a Hill coefficient of approximately 3.0, implying sequential kinase-domain activation beyond dimeric units. We present data for a model in which cooperative activation includes the intersubunit 'capture' of regulatory segments. Such a capture interaction is seen in a crystal structure that shows extensive contacts between the regulatory segment of one kinase and the catalytic domain of another. These interactions are mimicked by a natural inhibitor of CaMKII. Our results show that a simple coincidence-detection model cannot be operative and point to the importance of kinetic dissection of the frequency-response mechanism in future experiments.
Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation.,Chao LH, Pellicena P, Deindl S, Barclay LA, Schulman H, Kuriyan J Nat Struct Mol Biol. 2010 Mar;17(3):264-72. Epub 2010 Feb 7. PMID:20139983[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chao LH, Pellicena P, Deindl S, Barclay LA, Schulman H, Kuriyan J. Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation. Nat Struct Mol Biol. 2010 Mar;17(3):264-72. Epub 2010 Feb 7. PMID:20139983 doi:10.1038/nsmb.1751
