Design principles of transcription factors with intrinsically disordered regions

Abstract

Transcription Factors (TFs) are proteins crucial for regulating gene expression. Effective regulation requires the TFs to rapidly bind to their correct target, enabling the cell to respond efficiently to stimuli such as nutrient availability or the presence of toxins. However, the search process is hindered by slow diffusive movement and the presence of `false' targets --DNA segments that are similar to the true target. In eukaryotic cells, most TFs contain an Intrinsically Disordered Region (IDR), which is commonly assumed to behave as a long, flexible polymeric tail composed of hundreds of amino acids. Recent experimental findings indicate that the IDR of certain TFs plays a pivotal role in the search process. However, the principles underlying the IDR's role remain unclear. Here, we reveal key design principles of the IDR related to TF binding affinity and search time. Our results demonstrate that the IDR significantly enhances both of these aspects. Furthermore, our model shows good agreement with experimental results, and we propose further experiments to validate the model's predictions.

References in corpus (10)

• Theoretical perspective on the glass transition and amorphous materials
• Intermittent search strategies
• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• How do proteins search for their specific sites on coiled or globular DNA
• Spatial effects on the speed and reliability of protein-DNA search
• Classes of fast and specific search mechanisms for proteins on DNA
• Dependence of DNA persistence length on ionic strength and ion type
• Measurement of the Phase Diagram of DNA Unzipping in the Temperature- Force Plane
• Kinetics of viral self-assembly: the role of ss RNA antenna
• Harnessing Avidity: Quantifying Entropic and Energetic Effects of Linker Length and Rigidity Required for Multivalent Binding of Antibodies to HIV-1 Spikes