Cryo-electron microscopy finally breaks the barrier of atomic resolution | Science

Cryo-electron microscopy finally breaks the barrier of atomic resolution | Science

Cryo-electron microscopy reveals atomic details of apoferritin, a hollow, globular protein compound that stores iron.

Paul Emsley / MRC Molecular Biology Laboratory

By Robert F. Service

If you want to map the most accurate parts of a protein, you only have a few options: You can convince millions of individual protein molecules to align crystals and analyze them using X-ray crystallography. Or, you can quickly freeze protein copies and bombard them with electrons, a less accurate method called cryo-EM. Now, for the first time, scientists have sharpened cryo-EM resolution to the atomic level, allowing them to pinpoint the locations of individual atoms in a variety of proteins with an accuracy that rivals X-ray crystallography.

“This is amazing,” says Melanie O’He, an expert in refrigeration and electronic applications at the University of Michigan, Ann Arbor. “To see this level of detail, it’s beautiful.” As the increased resolution reveals exactly how complex cellular devices carry out their functions, improvements in cryo-EM technology should yield countless new insights into biology.

To map protein structures, scientists have used X-ray crystallography since the late 1950s. By bombarding crystallized proteins with X-rays and analyzing the X-ray bounce method, scientists can determine the protein’s possible structure and shape. Decades of improvements in X-ray beams, detectors and computer power have made this approach fast and accurate. But this approach does not work well when proteins are exceptionally large, function in complexes such as ribosomes, or cannot be crystallized, as is the case with many proteins found in cell membranes.

In contrast, the researchers used cryogenic fire electrons to copy frozen proteins that did not need to be crystallized. Detectors record the deflections of electrons, and sophisticated software links images together to determine the structure and shape of proteins. Researchers in Japan had previously shown that they could narrow the resolution down to 1.54 angstroms – not quite to the point where they could distinguish individual atoms – in a gut protein called apoferritin, which binds and stores iron. Now, with the help of improvements in electron beam technology, detectors, and software, two groups of researchers – from the UK and Germany –I narrowed that down to 1.25 Angstroms or betterAnd the Sharp enough to locate individual atoms, They report today at nature.

The enhanced resolution could accelerate the switch to cryo-EM that is already underway among structural biologists. For now, this technology only works with unusually solid proteins. Next, the researchers will strive to achieve similar sharpening precision with large, less stiff protein complexes, such as the spliceosome, a massive complex of proteins and RNA molecules that cut “introns” from RNA destined to turn into proteins.

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