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50 years of allosteric interactions: the twists and turns of the models

Nature Reviews Molecular Cell Biology volume 14, pages 819–829 (2013)Cite this article

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Abstract

The concept of indirect or 'allosteric' interaction between topographically distinct sites, and the subsequent 1965 Monod-Wyman-Changeux (MWC) model for the conformational change mediating them, arose around 50 years ago. Many classic regulatory proteins (including haemoglobin, Asp transcarbamylase and nicotinic acetylcholine receptor) follow the central paradigm of the MWC model, which has been expanded and challenged as a result of novel technologies. Importantly, the concept of allosteric interaction has aided our understanding of human diseases and drug design.

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Figure 1
Figure 2: Models of allosteric interactions.
Figure 3: An example of a typical allosteric protein.
Figure 4: Diversity of allosteric mechanisms.

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Acknowledgements

The author thanks S. Edelstein for helpful comments and P. Taylor and Skaggs Foundation UCSD School of Pharmacy for support.

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  1. Collège de France and CNRS URA 2182, Institut Pasteur, 47 rue du Four Paris 7506, Paris, France

    Jean-Pierre Changeux

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  1. Jean-Pierre Changeux
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Correspondence to Jean-Pierre Changeux.

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The repeated units of a symmetrical oligomeric protein.

Quaternary structure

The arrangement of multiple folded protein units in a multisubunit oligomeric complex.

Rate-equilibrium free energy analysis

An analysis that provides information on transition-state structures. It revealed, for instance, the temporal sequence in which the different regions of an ion channel protein move during a closed–open conformational transition.

Selectionist model of protein regulation

(also interpreted as a 'Darwinian' mechanism). The ligand selectively stabilizes pre-existing conformations when it binds to the state for which it exhibits preferential affinity. That is, the variability of the conformations takes place before selection occurs.

Sigmoidal substrate saturation kinetics

A classic deviation from Michaelis–Menten hyperbolic kinetics, revealing the cooperative interaction between several identical binding sites, as is the case when oxygen binds haemoglobin.

Single-channel electrophysiology

This patch clamp technique affords high resolution of the detailed properties of single-ion channel currents from many cell types.

Startle disease

(also known as hyperekplexia or exaggerated surprise). A neurological disorder classically characterized by pronounced startle responses to tactile or acoustic stimuli and hypertonia, and caused by genetic mutations in a number of different genes (such as the gene encoding Gly receptor).

Temperature-jump measurements

A technique for measuring rapid chemical kinetics, in which the solution is rapidly heated, for example, by the output of a pulsed laser.

The free energy landscape paradigm of protein folding

A statistical description of a potential surface of a protein. It assumes that folding occurs through organizing an ensemble of structures rather than through only a few uniquely defined structural intermediates.

Wide-angle X-ray scattering measurements

(WAXS measurements). An X-ray-diffraction technique that is used to determine the crystalline structure of proteins.

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Changeux, JP. 50 years of allosteric interactions: the twists and turns of the models. Nat Rev Mol Cell Biol 14, 819–829 (2013). https://doi.org/10.1038/nrm3695

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