Single-molecule PIFE probes millisecond local structural dynamics of a disordered protein

Intrinsically disordered proteins (IDPs) are oftentimes viewed as proteins that cannot fold in non-denaturing conditions, and perhaps even act as random polymers. Importantly, this behavior is what allows IDPs to gain functional context upon binding different targets which lead to is co-folding. So are IDPs indeed random polymers? One of the random polymer-like features that have been found for IDPs is that they undergo an overall conformational reconfiguration in a slow as single microseconds. Is this true for all modes of structural dynamics? In this talk I will present my recent works on the study of structural dynamics of the IDP α-Synuclein (αSyn) using a single-molecule fluorescence-based modality that probes local structuring – PhotoIsomerization-related Fluorescence Enhancement (PIFE). I will show that while non-local structural dynamics occur in hundreds of nanoseconds, local structural dynamics occur in milliseconds. This work shows that αSyn presents structural dynamics that deviates from what's commonly grasped for IDPs, which may assist it in promoting its binding-cofolding structure-function relationship.