Quantitative Aspects of Allosteric Mechanisms

The aim of this monograph is to summarize the essential features which characterize the behavior of regulatory systems. Firstly we discuss the laws which govern ligand binding in thermodynamic terms. The basic cooperative and allosteric phenomena are des­ cribed in thermodynamic terms without assuming any particular mo­ del. Then the molecular models developed by Monod, Wyman and Changeux and by Koshland, Nemethy and Filmer are presented in detail. Special emphasis has been given to the analysis of the Hill coefficient and its meaning both in thermodynamic terms and in terms of the two allosteric models: the concerted model of Monod, Wyman and Changeux and the sequential model of Koshland, Nemethy and Filmer. Special types of cooperativities are dis­ cussed in some detail namely, cooperativity stemming from ligand­ coupled protein association or dissociation, negative cooperati­ vity and half-of-the-sites reactivity. A slightly extended space was devoted to the discussion of negative cooperativity and half­ of-the-sites reactivity, since the existence of these phenomena and their possible biological importance is less of a common knowledge than positive cooperativity. This monograph does not attempt to be a review of specific examples analyzed according to one model or another. Rather, an attempt is made to provide the reader with the quantitative tools to analyze any specific regulatory system. Last but not least, I would like to thank Prof. F. W. Dahlquist from the Institute of Molecular Biology, the University of Oregon (Eugene) and Prof. D. E. Koshland, Jr.

Contenu

1 Basic Concepts of Allosteric Control.- 2 The Structure of Multisubunit Proteins.- I. General Principles.- II. Other Types of Protein Assemblies.- 3 Cooperativity in Multisubunit Proteins - The Basic Concepts.- I. The Hill Equation.- II. The General Adair Equation.- III. The Statistical Correction.- IV. The Hill Coefficient in Terms of Intrinsic Ligand Affinities.- V. The Hill Coefficient at 50% Ligand Saturation.- VI. The Maximal Hill Coefficient.- VII. The Limiting Values of the Hill Slope.- VIII. The Allosteric Dimer.- IX. The Multi-Dimer Case.- X. The Allosteric Tetramer.- XI. The General Tetrameric Case.- 4 The Energy of Subunit Interactions.- I. Determination of Intersubunit Interaction Energy.- II. The Hill Coefficient and the Intersubunit Interaction Energy.- III. The Meaning of Intersubunit Energy of Interaction.- 5 Molecular Models for Cooperativity and Allosteric Interactions.- I. Introduction.- II. The Monod-Wyman-Changeux (MWC) Concerted Model.- 1. Basic Assumptions of the Concerted Model.- 2. The Allosteric Dimer Analyzed by the MWC Model.- 3. Allosteric Inhibition and Allosteric Activation in the MWC Model.- 4. The General Case.- 5. Phenomena Explained by the Concerted Model.- 6. Cooperativity in the Monod-Wyman-Changeux Model.- III. The Koshland-Némethy-Filmer (KNF) Sequential Model.- 1. Basic Assumptions of the Sequential Model.- 2. The Allosteric Dimer Analyzed by the KNF Model.- 3. Allosteric Activation and Allosteric Inhibition in the KNF Model - the Dimer Case.- 4. The KNF Model - the Tetramer Case.- 5. The Influence of the Intersubunit Binding Domains on the Nature of Subunit Interactions.- IV. The Conformational State of the Protein.- 1. Exclusive Binding in the MWC Model.- 2. The Nonexclusive Binding in the MWC Model.- 3. The Simple Sequential KNF Model.- 4. The General Sequential KNF Model.- 5. Measuring R?.- V. Comparison Between the KNF Model and the MWC Model.- 6 Special Types of Cooperative Systems.- I. Cooperativity Resulting from Ligand-Coupled Protein Association or Dissociation.- 1. Ligand-Coupled Monomer-Dimer Equilibrium.- 2. The General Case.- II, Negative Cooperativity.- III. Protein Association and Dissociation Coupled to Ligand Binding.- 1, Dimerization Coupled to Ligand Binding.- 2. Monomer Multimer Equilibrium Coupled to Ligand Binding.- References.