Structure determination by micro-crystal 3D electron diffraction allows structure determination from minute crystals, 1000-times smaller than current X-ray diffraction methods, and has been used in the inorganic community for about 15 years. A few years ago, MicroED was extended to protein crystals and crystals of organic molecules, developments that led to that the method was selected as runner-up breakthrough of the year 2018 by the journal Science.


Determination of protein structures is very challenging and, so far, MicroED has only been used to re-determine structures that have already been solved previously by other methods. In this study, the teams from Stockholm University were able to for the first time use MicroED to solve and model a new protein structure, an oxidase enzyme with a di-metal cofactor.


Despite the current limitations of macromolecular MicroED, the protein structure could be accurately built and refined to a resolution of 3.0 Å, revealing new biochemical insight. The results show that MicroED has the potential to become an important general tool for studying the structure and function of proteins.



The study “Solving a new R2lox protein structure by microcrystal electron diffraction” was published in the journal Science Advances on Aug 7.




Figure 1. A & B: Thin crystal plates used for data collection. C & D: Electron diffraction data


Figure 2. A: Electrostatic scattering potential map. B: Protein model revealing a ligand-binding cavity.


Martin Högbom Lab