Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation
Abstract The insulin and insulin‐like growth factor 1 receptors activate overlapping signalling pathways that are critical for growth, metabolism, survival and longevity. Their mechanism of ligand binding and activation displays complex allosteric properties, which no mathematical model has been abl...
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| Format: | Article |
| Language: | English |
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Springer Nature
2009-02-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2008.78 |
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| _version_ | 1849225795961094144 |
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| author | Vladislav V Kiselyov Soetkin Versteyhe Lisbeth Gauguin Pierre De Meyts |
| author_facet | Vladislav V Kiselyov Soetkin Versteyhe Lisbeth Gauguin Pierre De Meyts |
| author_sort | Vladislav V Kiselyov |
| collection | DOAJ |
| description | Abstract The insulin and insulin‐like growth factor 1 receptors activate overlapping signalling pathways that are critical for growth, metabolism, survival and longevity. Their mechanism of ligand binding and activation displays complex allosteric properties, which no mathematical model has been able to account for. Modelling these receptors’ binding and activation in terms of interactions between the molecular components is problematical due to many unknown biochemical and structural details. Moreover, substantial combinatorial complexity originating from multivalent ligand binding further complicates the problem. On the basis of the available structural and biochemical information, we develop a physically plausible model of the receptor binding and activation, which is based on the concept of a harmonic oscillator. Modelling a network of interactions among all possible receptor intermediaries arising in the context of the model (35, for the insulin receptor) accurately reproduces for the first time all the kinetic properties of the receptor, and provides unique and robust estimates of the kinetic parameters. The harmonic oscillator model may be adaptable for many other dimeric/dimerizing receptor tyrosine kinases, cytokine receptors and G‐protein‐coupled receptors where ligand crosslinking occurs. |
| format | Article |
| id | doaj-art-ca50fc2ca65d492b8bbc2b3fcd258d39 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2009-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-ca50fc2ca65d492b8bbc2b3fcd258d392025-08-24T11:58:59ZengSpringer NatureMolecular Systems Biology1744-42922009-02-015111210.1038/msb.2008.78Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activationVladislav V Kiselyov0Soetkin Versteyhe1Lisbeth Gauguin2Pierre De Meyts3Receptor Systems Biology Laboratory, Hagedorn Research InstituteReceptor Systems Biology Laboratory, Hagedorn Research InstituteReceptor Systems Biology Laboratory, Hagedorn Research InstituteReceptor Systems Biology Laboratory, Hagedorn Research InstituteAbstract The insulin and insulin‐like growth factor 1 receptors activate overlapping signalling pathways that are critical for growth, metabolism, survival and longevity. Their mechanism of ligand binding and activation displays complex allosteric properties, which no mathematical model has been able to account for. Modelling these receptors’ binding and activation in terms of interactions between the molecular components is problematical due to many unknown biochemical and structural details. Moreover, substantial combinatorial complexity originating from multivalent ligand binding further complicates the problem. On the basis of the available structural and biochemical information, we develop a physically plausible model of the receptor binding and activation, which is based on the concept of a harmonic oscillator. Modelling a network of interactions among all possible receptor intermediaries arising in the context of the model (35, for the insulin receptor) accurately reproduces for the first time all the kinetic properties of the receptor, and provides unique and robust estimates of the kinetic parameters. The harmonic oscillator model may be adaptable for many other dimeric/dimerizing receptor tyrosine kinases, cytokine receptors and G‐protein‐coupled receptors where ligand crosslinking occurs.https://doi.org/10.1038/msb.2008.78activation mechanismbinding kineticsharmonic oscillator modelinsulin receptormathematical modelling |
| spellingShingle | Vladislav V Kiselyov Soetkin Versteyhe Lisbeth Gauguin Pierre De Meyts Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation Molecular Systems Biology activation mechanism binding kinetics harmonic oscillator model insulin receptor mathematical modelling |
| title | Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation |
| title_full | Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation |
| title_fullStr | Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation |
| title_full_unstemmed | Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation |
| title_short | Harmonic oscillator model of the insulin and IGF1 receptors’ allosteric binding and activation |
| title_sort | harmonic oscillator model of the insulin and igf1 receptors allosteric binding and activation |
| topic | activation mechanism binding kinetics harmonic oscillator model insulin receptor mathematical modelling |
| url | https://doi.org/10.1038/msb.2008.78 |
| work_keys_str_mv | AT vladislavvkiselyov harmonicoscillatormodeloftheinsulinandigf1receptorsallostericbindingandactivation AT soetkinversteyhe harmonicoscillatormodeloftheinsulinandigf1receptorsallostericbindingandactivation AT lisbethgauguin harmonicoscillatormodeloftheinsulinandigf1receptorsallostericbindingandactivation AT pierredemeyts harmonicoscillatormodeloftheinsulinandigf1receptorsallostericbindingandactivation |