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.

Structural basis of sequential and concerted cooperativity / Morea, Veronica; Angelucci, Francesco; Tame, Jeremy R. H.; Di Cera, Enrico; Bellelli, Andrea. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:11(2022), p. 1651. [10.3390/biom12111651]

Structural basis of sequential and concerted cooperativity

Andrea Bellelli
Conceptualization
2022

Abstract

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.
2022
KNF model; MWC model; allostery; heterotropic regulation; ligands; allosteric regulation; kinetics; proteins
01 Pubblicazione su rivista::01a Articolo in rivista
Structural basis of sequential and concerted cooperativity / Morea, Veronica; Angelucci, Francesco; Tame, Jeremy R. H.; Di Cera, Enrico; Bellelli, Andrea. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:11(2022), p. 1651. [10.3390/biom12111651]
File allegati a questo prodotto
File Dimensione Formato  
Morea_Structural _2022.pdf

accesso aperto

Note: articolo
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.44 MB
Formato Adobe PDF
2.44 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1660724
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact