New cryo-EM tool visualizes biomolecules at near-atomic level

By The Science Advisory Board staff writers

September 8, 2022 -- German researchers have used cryo-electron microscopy (cryo-EM) to visualize biomolecules at the atomic level, combining cryo-EM with a method used in materials research to observe protein building blocks in their natural environment in a snap-frozen state.

The team from Forschungszentrum Jülich and Heinrich Heine University Düsseldorf have combined cryo-EM with integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM).

In a study published on September 5 in the journal Nature Methods, the scientists applied iDPC-STEM to two cryo-EM test specimens: keyhole limpet hemocyanin (KLH) and tobacco mosaic virus (TMV). The micrographs showed complete contrast transfer to high resolution and enabled the cryo-EM structure determination for KLH at 6.5 Å and 3.5 Å for TMV using single-particle reconstruction methods.

The findings demonstrate that STEM imaging in general and the iDPC-STEM approach in particular can be applied to vitrified single-particle specimens to determine near-atomic resolution cryo-EM structures of biological macromolecules. This expands the possibilities for structural analysis, especially for heterogeneous, nonuniform samples or single particles when averaging capabilities are limited, the researchers noted.

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