Cryo-EM reaches yet another milestone – Comments on two recent cryo-EM atomic resolution studies

1 Jun 2020

Two studies published during last two weeks have reported that single particle cryo-EM data can be now resolved to 1.20Å or 1.25Å, respectively. The groups of Sjors H.W. Scheres (LMB-MRC, Cambridge) and Holger Stark (MPI Göttingen) have for the first time shown that atomic resolution is attainable by single particle cryo-EM. The cryo-EM maps of apoferritin utilized as a model system in both studies reveal densities of single atoms including the hydrogens. The single particle cryo-EM thus becomes a method capable of reaching atomic resolution. Both studies stress that the use of the electron source with minimal energy dispersion of the emitted electrons is a key for obtaining cryo-EM maps with <1.5Å resolution. This is achieved by utilization of the cold field emission gun (CFEG)  or standard Schottky field emission gun and monochromator.  Different strategies have been implemented to suppress the optical aberrations which play crucial role at resolutions <1.5Å. The group of H. Stark utilized the newly developed image corrector referenced as BCOR in their Titan Krios microscope to minimize the aberrations directly during data acquisition, whereas the group of S.H.W. Scheres used standard Titan Krios microscope without image corrector and deconvolved the optical aberrations at the level of the data processing within their Relion software. In addition, the study performed at LMB-MRC Cambridge utilizes image filter for filtering out of the inelastically scattered electrons and last generation of the direct electron detector Falcon4. Although the number of particles required to reach the 1.2Å cryo-EM maps differ between the two studies, both papers agree that 1.6-2.0Å resolution maps shall be attainable on the currently standard 300kV cryo-TEMs, which are not equipped with the presented technical advancements.

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