Scientists at the University of California, Los Angeles (UCLA), have developed a solution that allows cryo-electron microscopy (cryo-EM) to generate high-quality images of smaller protein molecules. Cryo-EM is a technique that enables the visualization of the atomic structure of biological molecules with high resolution. Previously, cryo-EM was only effective for visualizing large molecules, but this new breakthrough expands its capabilities.

The researchers created a protein structure in the form of a 20-nanometer cube, called a scaffold, with tripod-like protrusions to hold the small proteins in place. During processing, the scaffold can be digitally removed from the image, generating a 3D image solely of the small protein being analyzed. This advancement is significant for the study of small to medium-sized proteins, as they are crucial in the search for potential new drugs.

The team tested their method using cryo-EM to observe the atomic structure of a protein called KRAS, which is involved in approximately 25% of human cancers. This observation could aid in the development of drugs that can neutralize the cancer-causing abilities of KRAS by targeting specific locations in the protein.

This research opens up possibilities for exploring the atomic structures of smaller proteins and identifying targets for therapeutic purposes. Cryo-EM works by sending an electron beam through frozen samples of material and producing thousands of 2D photographs of the molecules from different angles. By reconciling these photographs, a high-resolution 3D image of a single molecule is generated.

The article detailing this research was published in the Proceedings of the National Academy of Sciences.

– Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2305494120