Cryo-electron microscopy (cryo-EM) is a powerful tool for exploring the structure and function of biomolecules at high resolution. In recent years, cryo-EM has revolutionized structural biology, providing insights into the mechanisms of many important biological processes.
Cryo-electron microscopy is based on the principle that when a sample is cooled to very low temperatures, the molecules in the sample will become immobilized and will retain their three-dimensional structure. This makes it possible to image the sample with high resolution using an electron microscope.
In order to obtain images with sufficient resolution to visualize individual atoms, it is necessary to use an electron microscope with extremely high magnification power and/or apply advanced image processing techniques. However, even with these advances, cryo-EM remains challenging due to the inherent flexibility of biomolecules and the need for large numbers of molecules in the sample to achieve statistically meaningful results.
Despite these challenges, cryo-EM has yielded some remarkable successes in recent years. One notable example is the determination of the atomic structure of HIV capsid protein by David Baker and colleagues (Science 2009). This work not only provided insights into how HIV infects cells, but also led to the development of new drugs that target HIV capsid proteins. Other examples include studies of ribosomes (Nature 2010), membrane proteins (Nature 2011), viruses (Science 2012), and enzymes (Nature 2013).
As technology continues to improve, it is likely that cryo-EM will play an increasingly important role in Structural Biology and other fields where high-resolution imaging is needed.