Intrinsically disordered regions are poised to act as sensors of cellular chemistry

Intrinsically disordered proteins and protein regions (IDRs) are abundant in eu-karyotic proteomes and play a wide variety of essential roles. Instead of folding into a stable structure, IDRs exist in an ensemble of interconverting conforma-tions whose structure is biased by sequence-dependent interactions. The ab-sence of a stable 3D structure, combined with high solvent accessibility, means that IDR conformational biases are inherently sensitive to changes in their environment. Here, we argue that IDRs are ideally poised to act as sensors and actuators of cellular physicochemistry. We review the physical principles that underlie IDR sensitivity, the molecular mechanisms that translate this sensi-tivity to function, and recent studies where environmental sensing by IDRs may play a key role in their downstream function.

Automated summary

Intrinsically disordered proteins and protein regions (IDRs) play essential roles in eukaryotic organisms. Unlike folded proteins, IDRs exist in a conformational ensemble influenced by sequence-dependent interactions. The absence of a stable 3D structure and high solvent accessibility make IDRs inherently sensitive to environmental changes, allowing them to act as sensors and actuators of cellular physicochemistry.