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. 

Topics from this paper

The structural basis of allosteric regulation in proteins
TLDR
Analysis of experimentally determined models of protein 3D structures, using either X‐ray crystallography or NMR spectroscopy, have revealed some of the mechanisms involved in allosteric regulation of protein function. Expand
Deciphering General Characteristics of Residues Constituting Allosteric Communication Paths
TLDR
The detailed analysis of the general character of allosteric communication paths enables to better understand the mechanism of allostery and can be used in for the design of new generations of drugs. Expand
Direct observation in solution of a preexisting structural equilibrium for a mutant of the allosteric aspartate transcarbamoylase
TLDR
The cooperative binding of aspartate in as partate transcarbamoylase appears to result from the combination of the preexisting quaternary structure equilibrium with local changes induced by CP binding, a central postulate of the Monod, Wyman, and Changeux model. Expand
Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation
TLDR
Four major receptor families enable cells to respond to chemical and physical signals from their proximal environment, and recent studies point to common mechanisms governing the allosteric transitions of these receptors, including the impact of oligomerization, pre-existing and functionally distinct conformational ensembles, intrinsically disordered regions, and the occurrence ofallosteric modulatory sites. Expand
Allosteric mechanisms can be distinguished using structural mass spectrometry
TLDR
It is demonstrated that structural MS offers a way to break this impasse by providing the full distribution of ligand-bound states of a protein complex, and it is possible to determine all the binding constants of a ligand to a highly multimeric cooperative system, and thereby infer its allosteric mechanism. Expand
Allosteric modulation as a unifying mechanism for receptor function and regulation
TLDR
Four major receptor families enable cells to respond to chemical and physical signals from their proximal environment, and recent studies point to common mechanisms governing the allosteric transitions of these receptors, including the impact of oligomerization, pre‐existing and functionally distinct conformational ensembles, intrinsically disordered regions, and the occurrence ofallosteric modulatory sites. Expand
Allosteric receptors after 30 years
The history of the allosteric concept is traced from its origins in studies on regulatory enzymes, repressors, membrane proteins, and hemoglobin to its recent applications concerning ionotropic andExpand
Allosteric Mechanism of Pyruvate Kinase from Leishmania mexicana Uses a Rock and Lock Model*
TLDR
The results presented here illustrate how conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control. Expand
Allosteric regulation of pentameric ligand-gated ion channels
TLDR
The present results suggest that ion gating involves a large structural reorganization of the molecule mediated by two distinct quaternary transitions, a global twisting and the blooming of the extracellular domain, which can be modulated by ligand binding at the topographically distinct orthosteric and allosteric sites. Expand
Computational approaches to investigating allostery.
TLDR
How the models of allostery have evolved from their initial formulation in the sixties to the current views, which more fully account for the roles of the thermodynamic and dynamic properties of the system are outlined. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 61 REFERENCES
Allosteric proteins and cellular control systems.
TLDR
The biological activity of many proteins is controlled by specific metabolites which do not interact directly with the substrates or products of the reactions, and it is suggested that this mechanism plays an essential role in the regulation of metabolic activity. Expand
Allosteric Receptors after 30 Years
TLDR
The roles of natural mutations and site-directed mutations in studying the mechanisms of activation and desensitization are reviewed, including the insights derived from constitutively active receptors and gain-of-function mutations. Expand
On the cooperativity of biological membranes.
TLDR
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. Expand
Extensions of the Allosteric Model for Haemoglobin
TLDR
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. Expand
Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins.
TLDR
The new findings suggest an expansion of the classical ternary complex model of receptor action to include an explicit isomerization of the receptors from an inactive to an active state which couples to the G protein ('allosteric ternARY complex model'). Expand
Conformational spread: the propagation of allosteric states in large multiprotein complexes.
  • D. Bray, T. Duke
  • Chemistry, Medicine
  • Annual review of biophysics and biomolecular structure
  • 2004
TLDR
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. Expand
Mechanisms of Cooperativity and Allosteric Regulation in Proteins
Preface 1. Introduction 2. Haemoglobin: Dependence of allosteric equilibrium on spin state and coordination of the haem iron 3. Haemocyanin: Dependence of allosteric equilibrium on coordination andExpand
G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology
TLDR
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. Expand
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 byExpand
Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis
TLDR
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. Expand
...
1
2
3
4
5
...