An allosteric model of calmodulin explains differential activation of PP2B and CaMKII
- European Molecular Biology Laboratory–European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, United Kingdom
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Communicated by Jean-Pierre Changeux, Institut Pasteur, Paris, France, May 15, 2008 (received for review January 15, 2008)
Abstract
Calmodulin plays a vital role in mediating bidirectional synaptic plasticity by activating either calcium/calmodulin-dependent protein kinase II (CaMKII) or protein phosphatase 2B (PP2B) at different calcium concentrations. We propose an allosteric model for calmodulin activation, in which binding to calcium facilitates the transition between a low-affinity [tense (T)] and a high-affinity [relaxed (R)] state. The four calcium-binding sites are assumed to be nonidentical. The model is consistent with previously reported experimental data for calcium binding to calmodulin. It also accounts for known properties of calmodulin that have been difficult to model so far, including the activity of nonsaturated forms of calmodulin (we predict the existence of open conformations in the absence of calcium), an increase in calcium affinity once calmodulin is bound to a target, and the differential activation of CaMKII and PP2B depending on calcium concentration.
Footnotes
- *To whom correspondence should be addressed. E-mail: lenov{at}ebi.ac.uk
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Author contributions: M.I.S. and N.L. designed research; M.I.S. and N.L. performed research; M.I.S. and S.J.E. analyzed data; and M.I.S., S.J.E., and N.L. wrote the paper.
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The authors declare no conflict of interest.
- © 2008 by The National Academy of Sciences of the USA
