Native State Conformational Dynamics of Disordered Protein Respond to Chemical Environment

Abstract

Many eukaryotic proteins are predicted to be intrinsically disordered meaning that they lack stable secondary and tertiary structure. Such intrinsically disordered proteins (IDPs) are extremely flexible and exhibit large conformational fluctuations in their native state. Despite lacking the “lock and key” interfaces of folded proteins, IDPs are biologically functional mediating essential cellular functions like controlling access to the nucleus and synaptic vesicles. IDPs are particularly prevalent in signal transduction where many cell surface proteins contain long disordered cytosolic domains. Previously we found differences in the native state conformational dynamics using single molecule analysis. Some IDPs are truly random coils while the other showed a stochastic switching among distinct conformational states, which was indistinguishable in the ensemble measurements due to averaging of many molecules. Here we have combined single molecule and ensemble methods to characterize the solubility landscape and molecular details of polymer dynamics in different ionic compositions, phosphorylation states, and protein-protein interactions. With the ability to change structural dynamics in response to chemical environments, IDPs exhibit large structural variations which maybe linked to physiological functions.