British and German scientists have used frozen mirrors to obtain the clearest imageof yet of a protein and identify for the first time a single atom, further cementing the technology’s dominance in mapping protein 3D shapes, the website of the British journal Nature reported recently. The “game-changing” technology promises to allow scientists to detect how proteins work with unprecedented clarity, creating drugs with fewer side effects and better side effects.
The latest technology, which has a resolution of 1.2 E (1 Emix x 10-10 m), clearly shows the position of individual atoms in a protein, which is particularly useful for understanding how enzymes work and discovering drugs that inhibit their activity. “Atomic resolution is a real milestone,” said John Rubenstein, a structural biologist at the University of Toronto in Canada. “
X-ray crystal diffraction was the primary method of studying proteins, but its sample preparation process is long and does not apply to all protein molecules. Cryo-EM is a “back-up” and is also known as cryogenic electron microscope. It can image protein structures at high resolution by e-emission electrons into instantaneously frozen samples. Frozen mirrors have been around for decades, and their resolution has been increasing with technological progress.
To further improve the resolution of the frozen electroscope, the Holger Stark team at the Max Planck Institute for Biophysical Chemistry and the Shoth Schhelos team at the University of Cambridge, UK, studied a protein called deferrin, which had previously been recorded at a resolution of 1.54 E.
In the latest study, the Stark team obtained an image with a resolution of 1.25 E, and the British team obtained a resolution of 1.2 E structure is also very complete. They say they can distinguish between a single hydrogen atom in a protein and surrounding water molecules. Stark believes that further improvements to the technology could bring the resolution to 1 E.
The two teams also tested their latest technology on a protein called GABAA receptor. GABAA receptors are targets for general anesthesia, anxiety drugs, etc.
These breakthroughs are expected to strengthen the position of cryoscopes as the preferred tool for most structural studies, Schhelos said. According to Stark, X-ray crystal diffraction still has its unique appeal, “and each technology has its own merits.”