Work

DNA‐Induced Entropic Gain Triggers an Allosteric Switch for Biomolecular Condensation of Heat Shock Transcription Factor 1

Year: 2026

Type: article

Abstract: The molecular logic of how site-specific DNA recognition by a transcription factor (TF) is transduced into macroscopic protein condensation remains a fundamental puzzle in chemical biology. Here, we unveil that the structured DNA-binding domain (DBD) of a TF acts as an entropic switch to regulate the release of the intrinsically disordered region (IDR). Using high-resolution solution NMR spectroscopy, we demonstrate that DNA binding significantly shifts the conformational equilibrium of the DBD toward a highly dynamic state. This conformational shift allosterically triggers the release of the IDR, thereby promoting macroscopic biomolecular condensation via multivalent interactions between the IDR and other molecules. Our findings define a mechanism of entropy-driven allostery, providing a structural and thermodynamic basis for how DNA-encoded information is transduced into macroscopic phase behavior.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.7340537

Authors: Soichiro Kawagoe, Hiroyuki Kumeta, Tomohide Saio

Institutions: Tokushima University, Hokkaido University

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $5,510