Allosteric Mechanisms of Signal Transduction

@article{Changeux2005AllostericMO,
  title={Allosteric Mechanisms of Signal Transduction},
  author={Jean Pierre Changeux and Stuart J. Edelstein},
  journal={Science},
  year={2005},
  volume={308},
  pages={1424 - 1428}
}
Forty years ago, a simple model of allosteric mechanisms (indirect interactions between distinct sites), used initially to explain feedback-inhibited enzymes, was presented by Monod, Wyman, and Changeux. We review the MWC theory and its applications for the understanding of signal transduction in biology, and also identify remaining issues that deserve theoretical and experimental substantiation. 
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632 Citations

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References

SHOWING 1-10 OF 59 REFERENCES

Allosteric proteins and cellular control systems.

Allosteric receptors after 30 years

On the cooperativity of biological membranes.

The Monod-Wyman-Changeux of allosteric transitions in enzyme-substrate reactions to a membrane composed of identical units (protomers) is extended and it appears possible to have a first-order phase transition when the chemical potential of the substrate is varied, holding the temperature constant.

Extensions of the Allosteric Model for Haemoglobin

Numerical analysis yields a unique value for the allosteric constant showing that only the two state model can account for the behaviour of the protein.

Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins.

Conformational spread: The propagation of allosteric states in large multiprotein complexes

  • D. BrayT. Duke
  • Biology
    Annual review of biophysics and biomolecular structure
  • 2004
It is suggested that conformational spread could provide the basis of a solid-state «circuitry» in a living cell, able to integrate biochemical and biophysical events over hundreds of protein molecules.

G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology

  • G. Milligan
  • Biology, Chemistry
    Molecular Pharmacology
  • 2004
Key questions that remain to be addressed effectively include the prevalence and relevance of these in native tissues and the implications of heterodimerization for pharmacology and, potentially, for drug design.

New insights into allosteric mechanisms from trapping unstable protein conformations in silica gels.

To understand why the classical two-state allosteric model of Monod, Wyman, and Changeux explains cooperative oxygen binding by hemoglobin but does not explain changes in oxygen affinity by…

Mechanisms of cooperativity and allosteric regulation in proteins Edited by Max Perutz. Published 1990 by Cambridge University Press, New York, Melbourne. No. of pages: 102. ISBN: 0-521-38648-9. Price at Aug. 1990: $17.95

  • M. Perutz
  • Biology
    The Journal of Steroid Biochemistry and Molecular Biology
  • 1992

Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis

The proposed structure is a regular two-dimensional lattice in which the cytoplasmic ends of chemotactic-receptor dimers are inserted into a hexagonal array of CheA and CheW molecules, which creates separate compartments for adaptation and downstream signalling, and indicates a possible basis for the spread of activity within the cluster.
...