Mapping the Conformational Dynamics of the Scaffold Protein PSD-95

Scaffold proteins form a dynamic framework to organize signal transduction by conjoining modular protein-binding domains. Scaffolds contain folded domains that are well understood but also disordered regions, which provide a challenge to structural biology. The folded domain structures for the scaffold protein PSD-95 were long known but such fragmentary knowledge lacks methods to assemble these pieces. We used single-molecule FRET studies with multi-parameter fluorescence detection [1] and filtered fluorescence correlation spectroscopy [2, 3] to describe the native state ensemble of this canonical scaffold protein.