Solution Space Fingerprints of Intrinsically Disordered Regions

Abstract

Intrinsically disordered regions (IDRs) play pivotal roles in mediating protein function and interactions, yet little is known about the way they function within cells. The cellular environment is in constant flux, and a high degree of flexibility and surface area make IDRs highly sensitive to changes in their surrounding solution. We have developed an experimental framework to understand how complex solution environments alter IDR structure and function. We use a FRET-based reporter to measure IDR structural changes using dozens of different biologically-compatible solution conditions. We call our method Solution Space (SolSpace) Scanning. We have tested a wide variety of IDRs and have found each to have its own unique set of responses to changes in solution conditions, i.e., its own SolSpace “fingerprint.” These results underline the idea that the structure and function of an IDR cannot be understood in terms of its sequence alone, but can be fully understood only in the context of its environment. We are now placing labeled IDRs in live cells to test how their structure and behavior can be influenced by perturbations to the cell that change the cell's inner environment.