Bubble Vision

Turning a liability into an asset, cryo-electron microscopists exploit an artifact to probe protein structure.

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Cryo-electron microscopy (cryo-EM) is a powerful technique used to provide high-resolution images of biological specimens. But radiation from the electron beam also degrades the sample and occasionally causes the proteins in the frozen sample to form bubbles of hydrogen gas.

Normally “we go out of our way to avoid this kind of bubbling,” says James Conway, an electron microscopist at the University of Pittsburgh. But when colleagues of Alasdair Steven at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) came to him with a cryo-EM–damaged picture of a virus, he recognized the artifact right away as bubbling and wondered if it might be useful. The virus, a bacteriophage, was known to have a cylindrical “inner body” of protein within its shell, but the structure was hard to make out using conventional cryo-EM because the density of the protein is the same as that of the DNA surrounding ...

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