An allosteric model of calmodulin
[pdf version] [erratum] [supporting information]
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.
After publication (on 6 Oct 2010), we found that the published versions of figures 3 and 4 were incorrect versions which were erroneusly inserted during the final editing stage. We published an erratum and Nicolas Le Novère has also compiled a corrected pdf by appending the erratum to the original reprint.
On 22 June 2010 I was awarded the Christian Doppler Prize 2009 in Biology from the State of Salzburg (Austria) for this paper and for more theoretical work on allosteric regulation.
- BIOMD0000000183 - curated by Lukas Endler
- The Model also featured as "Model of the Month" on BioModels Database in March 2009, with a nice short overview article written by Lu Li.