A simple model for proteins with interacting domains. Applications to scanning calorimetry data

Area of Science:

• Biophysics
• Biochemistry
• Thermodynamics

Background:

• Multidomain proteins exhibit complex interactions influencing their stability and function.
• Interactions between protein domains can be quantified using thermodynamic parameters.
• Scanning calorimetry is a key technique for studying protein unfolding and domain interactions.

Purpose of the Study:

• To develop a thermodynamic model for interpreting scanning calorimetry data of proteins with interacting domains.
• To quantify the interface free energy (delta GAB) between interacting protein domains.
• To apply the model to understand domain communication in ligand binding and protein stability.

Main Methods:

• Formulation of a simple thermodynamic model incorporating interface free energy (delta GAB).
• Application of the model to analyze scanning calorimetry data from various proteins.
• Estimation of delta GAB values for specific protein interactions and ligand-dependent binding.

Main Results:

• Estimated delta GAB of -25,000 cal/mol for interactions in aspartate transcarbamoylase.
• Determined delta GAB of 0 for interactions between transmembrane and cytoplasmic domains of human erythrocyte band 3.
• Showed ligand-dependent delta GAB can lead to regulatory control of ligand binding by other domains.

Conclusions:

• The thermodynamic model effectively interprets calorimetric data for interacting protein domains.
• Interface free energy (delta GAB) plays a crucial role in protein stability and ligand binding.
• Domain interactions can significantly modulate ligand binding affinity, as demonstrated in phosphoglycerate kinase.