National Synchrotron Light Source Seminar

The synapse is a signal processing machine composed of thousands of proteins that detects and responds to neurotransmitter signals. Many of the critical protein interactions at the synapse are mediated by intrinsically‐disordered polypeptides. Disorder is a common feature of signaling proteins. More than one third of eukaryotic proteins are predicted to be completely or partially disordered. Understanding the role of disordered polypeptides is one of the remaining challenges for structural biology. As with membrane proteins, disordered protein samples are challenging to produce and characterize. Because disordered proteins lack a unique structure, ensemble sampling methods cannot describe their behavior. Our work measures single molecule fluorescence as a means of probing intrinsic dynamics and monitoring interactions between disordered proteins. This methodology has shed light on the protein interactions involved in synaptic vesicle fusion and we are now trying to describe the structure of the partially‐disordered, scaffold protein, PSD‐95.