Today, microscopy technology has made a revolutionary breakthrough-human beings have seen a single atom for the first time, and a whole new “universe” is about to come. This is all thanks to the emergence of cryogenic electron microscopes.
What is a cryo-electron microscope? It uses a molecular imaging technology that “can change the rules of the game”. So far it has produced the clearest image in history—atomic resolution map, and it has identified a single atom in a protein for the first time.
Through cryo-electron microscopy, researchers can see the details of the protein as never before, and thus understand its working principle. However, due to the strong flexibility of protein, these working principles cannot be easily known by other imaging technologies (such as X-ray crystal technology). of.
This breakthrough was achieved by two research teams in the UK and Germany in May 2020. The scientific community generally believes that the main tool for mapping the three-dimensional structure of proteins in the future will be cryo-electron microscopy. These structures will ultimately help researchers understand how proteins determine whether the human body is healthy or diseased, and help produce drugs with fewer side effects. .
Cryogenic electron microscopy is a decades-old technology that uses electron beams to image frozen biomolecules to obtain the three-dimensional structure of the molecule.
In 2013, with the advancement of the detection of reflected electron technology and the enhancement of image analysis software functions, the resolution of cryo-electron microscopes has been significantly improved, and a clearer protein structure than ever before has been obtained-almost the same as using X-ray crystal technology The obtained protein structure is the same.
X-ray crystal technology is an older technology. By using the scattering effect of electrons on X-rays, it can obtain the distribution of electron density in the crystal, and then analyze the position information of atoms, that is, the crystal structure. Scientists rely heavily on X-ray crystal technology to obtain atomic-resolution structural diagrams. However, it may take months to years for them to crystallize the protein, and many medically important proteins cannot form useful crystals. In contrast, cryo-electron microscopy only requires the protein to be in a purified solution.
The accuracy of the atomic resolution map can reach about 1.2 angstroms (1.2×10-10 meters), which is enough to accurately identify the position of a single atom in a protein. Seeing these structures clearly helps to understand how enzymes work, so that drugs that can block their activity can be effectively identified.
In order to improve the resolution of cryo-electron microscopy, the two teams studied an iron storage protein called ferritin. Because the protein has very good stability, it has become a test article for cryo-electron microscopy. Then, the research team used technological improvements to capture this ferritin more clearly.
With the breakthrough of cryo-electron microscope technology, it will be the tool of choice for most structural studies when scientists conduct structural studies in the future. Especially pharmaceutical companies eager to understand the atomic structure may be more inclined to use it.
Of course, X-ray crystal technology will retain a certain appeal. If a protein can be crystallized, then in a short period of time, it can be relatively effective to generate structure diagrams that bind to thousands of potential drugs. However, it still takes hours or even days for cryo-electron microscopy to generate enough data.
Therefore, each technology has its advantages and disadvantages. Cryogenic electron microscopy and X-ray crystal technology will give full play to their respective strengths to overcome difficulties in the microscopic world.
