Image by Campbell, Veesler et al. (2015) (CC BY 4.0)

Pushing the limits

Cryo-electron microscopy is allowing us to explore protein structures at increasing levels of detail.

Proteins perform many critical tasks within cells, and to do so, they must first fold into specific shapes. Being able to visualize these shapes can help scientists to understand how proteins work, and help them create drugs that can interact with the proteins to treat diseases.

The past few years have seen the rapid development of an imaging technique called single-particle cryo-electron microscopy (or cryoEM for short), and this technique is now increasingly used to investigate protein structures. First, proteins are embedded in a thin film of non-crystalline ice by rapidly cooling to around the temperature of liquid nitrogen (below −180°C). This traps the protein in the shape it has in solution. High-energy electrons are then transmitted through the protein sample and their interaction with the atoms in the protein is recorded by a direct electron camera. The analysis of a large series of images recorded in this way can be used to determine the approximate positions of the atoms in the protein.

Previously, single-particle cryoEM techniques have not produced a detailed enough protein structure to be useful to scientists interested in drug development. By refining these techniques, Melody Campbell, David Veesler and co-workers have now obtained the most detailed cryoEM protein structure to date — a structure of an enzyme complex that helps get rid of proteins that are misfolded or that have become too abundant. The structure is so detailed that it reveals the shapes of some small groups of atoms that stick out from the sides of amino acids in the enzyme complex (amino acids are the building blocks of enzymes and all other proteins). Moreover, the structure shows where individual water molecules are positioned around the protein.

The level of detail in the structure produced by Campbell, Veesler and co-workers is high enough to be useful to drug researchers. Furthermore, because only 10% of the images that were collected were used to produce the structure, future work will investigate whether incorporating more of the images could reveal structures in even greater detail.

To find out more

Read the eLife research paper on which this eLife Digest is based: “2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy” (March 11, 2015).

eLife is an open-access journal that publishes outstanding research in the life sciences and biomedicine.

The main text on this page was reused (with modification) under the terms of a Creative Commons Attribution 4.0 International License. The original “eLife digest” can be found in the linked eLife research paper.