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Biochim Biophys Acta. 2016 May;1860(5):868-878. doi: 10.1016/j.bbagen.2015.10.010. Epub 2015 Oct 22.

On the link between conformational changes, ligand binding and heat capacity.

Author information

1
Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit IQFR-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain.
2
Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit IQFR-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain; IIS Aragón, Zaragoza, Spain; Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
3
Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit IQFR-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain; Department of Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain; IIS Aragón, Zaragoza, Spain; Fundacion ARAID, Government of Aragon, Spain. Electronic address: adrianvc@unizar.es.

Abstract

BACKGROUND:

Conformational changes coupled to ligand binding constitute the structural and energetics basis underlying cooperativity, allostery and, in general, protein regulation. These conformational rearrangements are associated with heat capacity changes. ITC is a unique technique for studying binding interactions because of the simultaneous determination of the binding affinity and enthalpy, and for providing the best estimates of binding heat capacity changes.

SCOPE OF REVIEW:

Still controversial issues in ligand binding are the discrimination between the “conformational selection model” and the “induced fit model”, and whether or not conformational changes lead to temperature dependent apparent binding heat capacities. The assessment of conformational changes associated with ligand binding by ITC is discussed. In addition, the “conformational selection” and “induced fit” models are reconciled, and discussed within the context of intrinsically (partially) unstructured proteins.

MAJOR CONCLUSIONS:

Conformational equilibrium is a major contribution to binding heat capacity changes. A simple model may explain both conformational selection and induced fit scenarios. A temperature-independent binding heat capacity does not necessarily indicate absence of conformational changes upon ligand binding. ITC provides information on the energetics of conformational changes associated with ligand binding (and other possible additional coupled equilibria).

GENERAL SIGNIFICANCE:

Preferential ligand binding to certain protein states leads to an equilibrium shift that is reflected in the coupling between ligand binding and additional equilibria. This represents the structural/energetic basis of the widespread dependence of ligand binding parameters on temperature, as well as pH, ionic strength and the concentration of other chemical species.

KEYWORDS:

Allostery; Conformational change; Conformational selection and induced fit; Heat capacity change; Isothermal titration calorimetry; Ligand binding

PMID:
26476135
DOI:
10.1016/j.bbagen.2015.10.010
[Indexed for MEDLINE]

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