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Structural Basis of Sequential and Concerted Cooperativity

Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the “concerted model” by Monod, Wyman, and Changeux in 1965. Since its incepti...

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Autores principales: Morea, Veronica, Angelucci, Francesco, Tame, Jeremy R. H., Di Cera, Enrico, Bellelli, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687781/
https://www.ncbi.nlm.nih.gov/pubmed/36359000
http://dx.doi.org/10.3390/biom12111651
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author Morea, Veronica
Angelucci, Francesco
Tame, Jeremy R. H.
Di Cera, Enrico
Bellelli, Andrea
author_facet Morea, Veronica
Angelucci, Francesco
Tame, Jeremy R. H.
Di Cera, Enrico
Bellelli, Andrea
author_sort Morea, Veronica
collection PubMed
description Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the “concerted model” by Monod, Wyman, and Changeux in 1965. Since its inception, this model of cooperativity was seen as distinct from and not reducible to the “sequential model” originally formulated by Pauling in 1935, which was developed further by Koshland, Nemethy, and Filmer in 1966. However, it is difficult to decide which model is more appropriate from equilibrium or kinetics measurements alone. In this paper, we examine several cooperative proteins whose functional behavior, whether sequential or concerted, is established, and offer a combined approach based on functional and structural analysis. We find that isologous, mostly helical interfaces are common in cooperative proteins regardless of their mechanism. On the other hand, the relative contribution of tertiary and quaternary structural changes, as well as the asymmetry in the liganded state, may help distinguish between the two mechanisms.
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spelling pubmed-96877812022-11-25 Structural Basis of Sequential and Concerted Cooperativity Morea, Veronica Angelucci, Francesco Tame, Jeremy R. H. Di Cera, Enrico Bellelli, Andrea Biomolecules Article Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the “concerted model” by Monod, Wyman, and Changeux in 1965. Since its inception, this model of cooperativity was seen as distinct from and not reducible to the “sequential model” originally formulated by Pauling in 1935, which was developed further by Koshland, Nemethy, and Filmer in 1966. However, it is difficult to decide which model is more appropriate from equilibrium or kinetics measurements alone. In this paper, we examine several cooperative proteins whose functional behavior, whether sequential or concerted, is established, and offer a combined approach based on functional and structural analysis. We find that isologous, mostly helical interfaces are common in cooperative proteins regardless of their mechanism. On the other hand, the relative contribution of tertiary and quaternary structural changes, as well as the asymmetry in the liganded state, may help distinguish between the two mechanisms. MDPI 2022-11-07 /pmc/articles/PMC9687781/ /pubmed/36359000 http://dx.doi.org/10.3390/biom12111651 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morea, Veronica
Angelucci, Francesco
Tame, Jeremy R. H.
Di Cera, Enrico
Bellelli, Andrea
Structural Basis of Sequential and Concerted Cooperativity
title Structural Basis of Sequential and Concerted Cooperativity
title_full Structural Basis of Sequential and Concerted Cooperativity
title_fullStr Structural Basis of Sequential and Concerted Cooperativity
title_full_unstemmed Structural Basis of Sequential and Concerted Cooperativity
title_short Structural Basis of Sequential and Concerted Cooperativity
title_sort structural basis of sequential and concerted cooperativity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687781/
https://www.ncbi.nlm.nih.gov/pubmed/36359000
http://dx.doi.org/10.3390/biom12111651
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