Despite modern advances in structural biology, structures of many biomedically relevant macromolecular assemblies remain out of reach or lack atomic resolution detail. Large crystals required for conventional crystallography experiments are a challenge to grow, and determination of structures from small or imperfect crystals by x-ray crystallography remains limited. Cryo-electron microscopy (cryo-EM) methods promise to bring new life to high-throughput approaches in macromolecular structure determination through methods like micro electron diffraction (MicroED). MicroED exploits the strong interaction between electrons and nano-scale three-dimensional crystals by leveraging emerging cryo-EM instrumentation against established crystallographic knowledge. These technological advances, coupled with the greater availability of advanced cryoEM instruments, present an opportunity for further improvement of high-throughput structure determination. The development of new and more efficient approaches to structure determination by MicroED allow us to determine structures from small, fragile, and imperfect crystals. We focus on infectious and/or toxic filamentous nanoassemblies associated with disease including prion structures. Through our efforts in determining these challenging structures, we find inspiration to guide the improvement and development of cryoEM techniques, particularly MicroED.

Atomic structures of infectious amyloid assemblies

2019 Spring National Meeting

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