Cryo-EM reconstructed map of a protein complex

A cross-section of a self-assembling scaffold adorned with proteins. Credit: Y. Liu et al./Proc. Natl Acad. Sci. USA

Molecular biology

Small proteins come into focus

Miniature scaffold hold proteins steady for cryo-electron microscopy.

Scientists have smashed a size limit on the range of proteins that can be imaged in 3D with electron microscopy.

Proteins can be reconstructed in 3D detail by photographing samples under a transmission electron microscope at temperatures below −150°C. This technique, known as cryo-electron microscopy, is used to image viruses and other structures that contain multiple protein molecules. But the technique is difficult to apply to individual proteins because of their small size.

Todd Yeates at the University of California, Los Angeles, and his colleagues developed a self-assembling scaffold that binds to multiple copies of a target protein. The researchers recorded large numbers of detailed 2D images of the protein-bedecked scaffold, and used the images to create a 3D reconstruction of the target. The technique allowed the team to determine the shape of a tiny engineered protein just one-third of the size of the previous limit.