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.
PubMed ID: 18669651
Projects: Kinetics on the move - Workshop 2016
Publication type: Not specified
Journal: Proc Natl Acad Sci U S A
Citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10768-73. doi: 10.1073/pnas.0804672105. Epub 2008 Jul 31.
Date Published: 31st Jul 2008
Registered Mode: Not specified
Created: 30th May 2016 at 18:14