Cooperative ligand binding is a fundamental property of many biological macromolecules, notably transport proteins, hormone receptors, and enzymes. Positive homotropic cooperativity, the form of cooperativity that has greatest physiological relevance, causes the ligand affinity to increase as ligation proceeds, thus increasing the steepness of the ligand binding isotherm. The measurement of the extent of cooperativity has proven difficult, and the most commonly employed marker of cooperativity, the Hill coefficient, originates from a structural hypothesis that has long been disproved. However, a wealth of relevant biochemical data has been interpreted using the Hill's coefficient, and is being used in studies on evolution and comparative physiology. Even a cursory analysis of the pertinent literature shows that several authors tried to derive from the Hill's coefficient more sound biochemical information, often unaware of each other. As a result, a perplexing array of equations interpreting the Hill's coefficient is available in the literature, each responding to specific simplifications or assumptions. In this work we summarize and try to order these attempts, and demonstrate that the Hill coefficient (i) provides a minimum estimate of the free energy of interaction, the other parameter used to measure cooperativity, and (ii) bears a robust statistical correlation to the population of incompletely saturated ligation intermediates. Our aim is to critically evaluate the different analyses that have been advanced to provide a physical meaning to the Hill coefficient, and possibly to select the most reliable ones to be used in comparative studies that may make use of the extensive but elusive information available in the literature.

On the measurement of cooperativity and the physico-chemical meaning of the hill coefficient / Bellelli, Andrea; Caglioti, Emanuele. - In: CURRENT PROTEIN & PEPTIDE SCIENCE. - ISSN 1389-2037. - 20:9(2019), pp. 861-872. [10.2174/1389203720666190718122404]

On the measurement of cooperativity and the physico-chemical meaning of the hill coefficient

Bellelli, Andrea
;
Caglioti, Emanuele
2019

Abstract

Cooperative ligand binding is a fundamental property of many biological macromolecules, notably transport proteins, hormone receptors, and enzymes. Positive homotropic cooperativity, the form of cooperativity that has greatest physiological relevance, causes the ligand affinity to increase as ligation proceeds, thus increasing the steepness of the ligand binding isotherm. The measurement of the extent of cooperativity has proven difficult, and the most commonly employed marker of cooperativity, the Hill coefficient, originates from a structural hypothesis that has long been disproved. However, a wealth of relevant biochemical data has been interpreted using the Hill's coefficient, and is being used in studies on evolution and comparative physiology. Even a cursory analysis of the pertinent literature shows that several authors tried to derive from the Hill's coefficient more sound biochemical information, often unaware of each other. As a result, a perplexing array of equations interpreting the Hill's coefficient is available in the literature, each responding to specific simplifications or assumptions. In this work we summarize and try to order these attempts, and demonstrate that the Hill coefficient (i) provides a minimum estimate of the free energy of interaction, the other parameter used to measure cooperativity, and (ii) bears a robust statistical correlation to the population of incompletely saturated ligation intermediates. Our aim is to critically evaluate the different analyses that have been advanced to provide a physical meaning to the Hill coefficient, and possibly to select the most reliable ones to be used in comparative studies that may make use of the extensive but elusive information available in the literature.
2019
adair equation; allostery; cooperativity; free energy of interaction; two-state model
01 Pubblicazione su rivista::01a Articolo in rivista
On the measurement of cooperativity and the physico-chemical meaning of the hill coefficient / Bellelli, Andrea; Caglioti, Emanuele. - In: CURRENT PROTEIN & PEPTIDE SCIENCE. - ISSN 1389-2037. - 20:9(2019), pp. 861-872. [10.2174/1389203720666190718122404]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1316329
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