public model
Model Identifier
BIOMD0000000183
Short description
Stefan2008 - calmodulin allostery

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.

This model is described in the article:

Stefan MI, Edelstein SJ, Le Novère N
Proc. Natl. Acad. Sci. U.S.A. 2008 Aug; 105(31): 10768-10773

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V3)
Related Publication
  • An allosteric model of calmodulin explains differential activation of PP2B and CaMKII.
  • Stefan MI, Edelstein SJ, Le Novère N
  • Proceedings of the National Academy of Sciences of the United States of America , 8/ 2008 , Volume 105 , pages: 10768-10773 , PubMed ID: 18669651
  • European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, United Kingdom.
  • 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.
Contributors
Melanie Stefan

Metadata information

is
BioModels Database MODEL9885984404
BioModels Database BIOMD0000000183
isDescribedBy
PubMed 18669651
hasTaxon
Taxonomy Mammalia
isPartOf
Reactome CaM pathway
KEGG Pathway Long-term potentiation
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated


Tags
Name Description Size Actions

Model files

BIOMD0000000183_url.xml SBML L2V3 representation of Stefan2008 - calmodulin allostery 440.72 KB Preview | Download

Additional files

BIOMD0000000183.pdf Auto-generated PDF file 1.73 MB Preview | Download
BIOMD0000000183.sci Auto-generated Scilab file 87.66 KB Preview | Download
BIOMD0000000183-biopax3.owl Auto-generated BioPAX (Level 3) 929.20 KB Preview | Download
BIOMD0000000183.vcml Auto-generated VCML file 511.81 KB Preview | Download
BIOMD0000000183-biopax2.owl Auto-generated BioPAX (Level 2) 500.85 KB Preview | Download
BIOMD0000000183.m Auto-generated Octave file 112.93 KB Preview | Download
BIOMD0000000183.svg Auto-generated Reaction graph (SVG) 557.00 bytes Preview | Download
BIOMD0000000183_urn.xml Auto-generated SBML file with URNs 437.36 KB Preview | Download
BIOMD0000000183.xpp Auto-generated XPP file 88.80 KB Preview | Download
BIOMD0000000183.png Auto-generated Reaction graph (PNG) 5.07 KB Preview | Download

  • Model originally submitted by : Melanie Stefan
  • Submitted: Aug 14, 2008 5:08:52 PM
  • Last Modified: Jun 4, 2014 12:22:28 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Jun 4, 2014 12:22:28 PM
    • Submitted by: Melanie Stefan
    • With comment: Current version of Stefan2008 - calmodulin allostery
  • Version: 1 public model Download this version
    • Submitted on: Aug 14, 2008 5:08:52 PM
    • Submitted by: Melanie Stefan
    • With comment: Original import of Stefan2007_calmodulin_allostery
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
species 2

calcium(2+) ; Calmodulin
0.0 mol
species 6

calcium(2+) ; Calmodulin
0.0 mol
species 7

calcium(2+) ; Calmodulin
0.0 mol
species 9

calcium(2+) ; Calmodulin
0.0 mol
Reactions
Reactions Rate Parameters
compartment_0*species_18*parameter_10/parameter_11^(1/2)

compartment_0*species_18*parameter_10/parameter_11^(1/2)
parameter_11 = 0.00396; parameter_10 = 48.3792936623125
compartment_0*parameter_15*species_2*species_33

compartment_0*parameter_15*species_2*species_33
parameter_15 = 3200000.0
compartment_0*parameter_17*species_2*species_50

compartment_0*parameter_17*species_2*species_50
parameter_17 = 4.6E7
compartment_0*parameter_4*species_13

compartment_0*parameter_4*species_13
parameter_4 = 0.0145
compartment_0*species_6*parameter_9*(parameter_11*parameter_12)^(1/2)

compartment_0*species_6*parameter_9*(parameter_11*parameter_12)^(1/2)
parameter_11 = 0.00396; parameter_9 = 1000000.0; parameter_12 = 0.00396
compartment_0*species_22*parameter_10/(parameter_11*parameter_12)^(1/2)

compartment_0*species_22*parameter_10/(parameter_11*parameter_12)^(1/2)
parameter_11 = 0.00396; parameter_10 = 48.3792936623125; parameter_12 = 0.00396
compartment_0*parameter_15*species_6*species_33

compartment_0*parameter_15*species_6*species_33
parameter_15 = 3200000.0
compartment_0*parameter_16*species_39

compartment_0*parameter_16*species_39
parameter_16 = 0.343
compartment_0*parameter_17*species_6*species_50

compartment_0*parameter_17*species_6*species_50
parameter_17 = 4.6E7
compartment_0*parameter_18*species_56

compartment_0*parameter_18*species_56
parameter_18 = 0.0013
compartment_0*parameter_1*species_7

compartment_0*parameter_1*species_7
parameter_1 = 8.32
compartment_0*parameter_0*species_7*species_1

compartment_0*parameter_0*species_7*species_1
parameter_0 = 1000000.0
compartment_0*parameter_1*species_12

compartment_0*parameter_1*species_12
parameter_1 = 8.32
compartment_0*species_9*parameter_9*(parameter_12*parameter_13)^(1/2)

compartment_0*species_9*parameter_9*(parameter_12*parameter_13)^(1/2)
parameter_13 = 0.00396; parameter_9 = 1000000.0; parameter_12 = 0.00396
compartment_0*parameter_15*species_9*species_33

compartment_0*parameter_15*species_9*species_33
parameter_15 = 3200000.0
Curator's comment:
(added: 27 Oct 2009, 13:35:00, updated: 27 Oct 2009, 13:35:00)
Reproduction of some of the results from figure 4 of the original publication. The results correspond to the figure in the corrigendum. All simulations were performed using SBML ODESolver using a PPB2 concentration of 0 M, a CamKII concentration of 7e-05 M resp. 0 M. The starting values for CamR and CamT were 9.7e-12 M resp. 2e-07 M. The integration was performed for 100 sec or until a steady state was reached.