Liang, Y.-L. et al. Nature http://dx.doi.org/10.1038/nature22327 (2017).

Impressive technical advances in cryo-electron microscopy (cryo-EM) are enabling researchers to solve ever-smaller protein complexes at improving resolutions. The recently developed 'Volta phase plate' is stirring excitement with its ability to collect single-particle cryo-EM images with improved contrast. Liang et al. used this phase plate to help solve the full-length, near-atomic-resolution structure of an activated class-B G-protein-coupled receptor (GPCR; calcitonin receptor) in complex with a peptide agonist and G protein, weighing just 150 kDa. Several GPCR structures have been solved using X-ray crystallography, but most of these required extensive engineering efforts; no activated, full-length class-B-receptor structures have been reported. The work thus demonstrates the potential of cryo-EM for structure determination of unmodified, wild-type GPCR complexes, which may be of particular interest for drug discovery.