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.- III. The Koshland-Némethy-Filmer (KNF) Sequential Model.- IV. The Conformational State of the Protein.- 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.- 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.