UCLA-Led Team Develops Key Improvement to Nobel Prize-Winning Technology of Cryo-Electron Microscopy (Cryo-EM); Modification Enables High-Quality Images of Smaller Proteins

An electron microscope image of scaffolds attached to the protein KRAS (background). The left circle highlights one imaging scaffold, the second displays the 3D structure of the imaging scaffold bound to KRAS, and the third shows a close-up of KRAS attached to the cancer drug AMG510. See larger image at end.

The scientists who received the 2017 Nobel Prize in chemistry were honored for their development of a technique called cryo-electron microscopy, or cryo-EM. The technology was revolutionary because it enabled scientists to see the atomic structure of biological molecules in high resolution. But cryo-EM still had a catch: It was only effective for imaging large molecules. Now, UCLA biochemists, working with pharmaceutical industry scientists, have developed a solution that will make it possible for cryo-EM to acquire high-quality images of smaller protein molecules also. The scientists engineered a 20-nanometer, cube-shaped protein structure, called a scaffold, with rigid tripod-like protrusions that hold the small proteins in place. The scaffold can be digitally removed from the picture when the imaging is being processed, leaving a composite 3D image of just the small protein scientists are analyzing.

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