When Proteins Go Rogue: Conformational Disorder in Cancer and Neurological Disease
Dr. Derek Wilson
Department of Chemistry
Tuesday, September 30, 2014
C2-361 (Reading Room)
Abstract: Looking at the beautiful X-ray crystallographic protein structures that are the focus of classical structural biology, one could be forgiven for believing that proteins just sit there and look pretty. But if they were truly as immobile and 'brick-like' as they appear in these images, most would be virtually non-functional. In fact, proteins are constantly undergoing thermally-driven conformational fluctuations - conformational dynamics - in which they briefly adopt higher energy structures that are critical to function. Virtuallly all of the processes that underlie biological activity - ligand binding, allostery, catalysis and functional control through modification - would be impossible without the ability to 'visit' alternate structures through dynamics. Don't believe me? Try getting your favorite hyperthermophile enzyme to work at room temperature (it won't... at least not very well)... But as vital as it may be, all this moving around, morphing from one shape to another is dangerous. What if these conformational fluctuations go too far? What if we get stuck in 'non-native' structures that are pathogenic? The answer is: Bad stuff happens. Usually to your neurons. In this talk, we'll discuss how we characterize high energy, transient structures in protein function and disease, with a view to 'pacifying' the danger they can sometimes represent.