Allostery and the Monod-Wyman-Changeux Model After 50 Years

The Monod-Wyman-Changeux (MWC) model was conceived in 1965 to account for the signal transduction and cooperative properties of bacterial regulatory enzymes and hemoglobin. It was soon extended to pharmacological receptors for neurotransmitters and other macromolecular entities involved in intracell...

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Veröffentlicht in:Annual review of biophysics 2012-06, Vol.41 (1), p.103-133
1. Verfasser: Changeux, Jean-Pierre
Format: Artikel
Sprache:eng
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Zusammenfassung:The Monod-Wyman-Changeux (MWC) model was conceived in 1965 to account for the signal transduction and cooperative properties of bacterial regulatory enzymes and hemoglobin. It was soon extended to pharmacological receptors for neurotransmitters and other macromolecular entities involved in intracellular and intercellular communications. Five decades later, the two main hypotheses of the model are reexamined on the basis of a variety of regulatory proteins with known X-ray structures: ( a ) Regulatory proteins possess an oligomeric structure with symmetry properties, and ( b ) the allosteric interactions between topographically distinct sites are mediated by a conformational transition established between a few preestablished states with conservation of symmetry and ligand-directed conformational selection. Several well-documented examples are adequately represented by the MWC model, yet a few possible exceptions are noted. New questions are raised concerning the dynamics of the allosteric transitions and more complex supramolecular ensembles.
ISSN:1936-122X
1936-1238
DOI:10.1146/annurev-biophys-050511-102222