3kk9
CaMKII Substrate Complex BCaMKII Substrate Complex B
Structural highlights
Function[Q9U6Q0_CAEEL] Role in locomotion and neuronal cell fate specification. Required for the regulation of synaptic density, egg laying, defecation, and meiotic maturation. Required for viability under chronic osmotic stress in which it acts downstream of osr-1. Regulates the synaptic trafficking of glr-1. Bidirectional modulator of neurotransmitter release with negative modulatory effects mainly mediated via slo-1 activation. May suppress the functional response to an internal pacemaker, perhaps by modulating the activity of the IP3 receptor.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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