Macromolecular crystallography using microcrystal electron diffraction

Microcrystal electron diffraction (MicroED) has recently emerged as a promising method for macromolecular structure determination in structural biology. Since the first protein structure was determined in 2013, the method has been evolving rapidly. Several protein structures have been determined and various studies indicate that MicroED is capable of (i) revealing atomic structures with charges, (ii) solving new protein structures by molecular replacement, (iii) visualizing ligand-binding interactions and (iv) determining membrane-protein structures from microcrystals embedded in lipidic mesophases. However, further development and optimization is required to make MicroED experiments more accurate and more accessible to the structural biology community. Here, we provide an overview of the current status of the field, and highlight the ongoing development, to provide an indication of where the field may be going in the coming years. We anticipate that MicroED will become a robust method for macromolecular structure determination, complementing existing methods in structural biology.

Automated summary

Microcrystal electron diffraction (MicroED) has emerged as a promising method for macromolecular structure determination in structural biology, showing capabilities in revealing atomic structures, solving new protein structures, visualizing ligand-binding interactions, and determining membrane-protein structures. Further development and optimization are needed to make MicroED experiments more accurate and accessible, but it is anticipated to become a robust method complementing existing methods in structural biology.