MWC model
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In biochemistry, the MWC model refers to the Concerted model (by opposition to the Sequential model, or KNF model) of allosteric transition, which was proposed by Jean-Pierre Changeux based on his PhD experiements, and described by Jacques Monod, Jeffries Wyman, and Jean-Pierre Changeux.
The main idea of the model is that regulated proteins, such as many enzymes and receptors, exist in different interconvertible states in the absence of any regulator. The ratio of the different conformational states is determined by thermal equilibrium. The regulators merely shift the equilibrium toward one state or another. For instance, an agonist will stabilise the active form of a pharmacological receptor. Phenomenologically, it look-likes the agonist provokes the conformational transition. One crucial feature of the model is the dissociation between the binding function (the ratio of protein bound to the regulator), and the state function (the ratio or protein under the activated state). In the models said of "induced-fit", those functions are identical.
The MWC model proved very popular in enzymology, physiology (hemoglobin) and pharmacology, although it has been shown inappropriate in a certain number of cases. Extension of the model have been proposed for lattice of proteins, for instance by Wyman or Duke, Le Novere and Bray.
References
- Changeux J.-P. (1964). Allosteric interactions interpreted in terms of quaternary structure. Brookhaven Symposia in Biology, 17: 232-249.
- Monod J., Wyman J., and Changeux J.-P. (1965). On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12: 88-118.
- Wyman J (1969). Possible allosteric effects in extended biological systems. J Mol Biol. 14:523-538.
- Edelstein SJ (1972). Extensions of the allosteric model for haemoglobin. Nature. 1971 230:224-227.
- Changeux JP, Edelstein SJ (1998). Allosteric receptors after 30 years. Neuron 21: 959-980.
- Duke TA, Le Novere N, Bray D (2001). Conformational spread in a ring of proteins: a stochastic approach to allostery. J Mol Biol. 308:541-553.
- Changeux JP, Edelstein SJ. (2005) Allosteric mechanisms of signal transduction. Science, 2005 Jun 3;308(5727):1424-8.
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