Coupling of Local Folding to Site-Specific Binding of Proteins to DNA

TLDR

Thermodynamic studies show that a large negative heat‑capacity change (ΔC°assoc) is central to site‑specific protein‑DNA recognition, highlighting the energetic implications of an induced‑fit model for DNA site recognition. By dissecting the large negative ΔC°assoc and entropy changes in protein‑ligand and protein‑DNA complexation, the authors identify a thermodynamic signature that signals local folding coupled to binding. The analysis estimates the number of residues that fold upon binding, matching structural data, and shows that these local folding transitions form key parts of the protein‑DNA interface.

Abstract

Thermodynamic studies have demonstrated the central importance of a large negative heat capacity change (Δ C ° assoc ) in site-specific protein-DNA recognition. Dissection of the large negative Δ C ° assoc and the entropy change of protein-ligand and protein-DNA complexation provide a thermodynamic signature identifying processes in which local folding is coupled to binding. Estimates of the number of residues that fold on binding obtained from this analysis agree with structural data. Structural comparisons indicate that these local folding transitions create key parts of the protein-DNA interface. The energetic implications of this "induced fit" model for DNA site recognition are considered.