Electron diffraction of 3D nanocrystals: an emerging technique in structural biology but also in material science and chemistry

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Electron diffraction of 3D nanometer sized crystals, most commonly named microED, has recently emerged as a new technique to solve the structure of both small organic molecules and proteins. MicroED is clearly a promising technique in structural biology, both quite easy to implement and very complementary to X-ray crystallography and single particle cryo-EM. Electrons are actually a very interesting probe for small samples as they strongly interact with matter, and more importantly, they deposit much less energy than X-rays per diffracted particle [4]. Sub-atomic resolution data can routinely be collected for small organic compounds and data up to 0.9 Å resolution have been obtained from protein crystals. However, a quick look at the Protein Data Bank shows that among the ~70 protein structures determined so far by microED, only 10 are not model proteins, indicating that microED is still far from routinely used in structural biology. The major bottleneck of the technique when applied to protein samples is to produce nano-crystals that do not exceed 200 to 300 nm in at least one dimension and to deposit them on a grid while keeping the minimum amount of solvent around them. Phasing can be done by either direct methods for sub-atomic resolution data or by molecular replacement but it could be difficult in some cases. Based on different type of samples (proteins, MOF, ...) studied at IBS, thanks to our hybrid pixel direct detector mounted on an F20 200 kV electron microscope, but also on other examples picked up in the literature, an overview of the main results of the technique will be made.