Transmission electron microscope imaging biomolecules flash-frozen in vitreous ice at cryogenic temperatures to solve near-atomic 3D structures.
Specifications & Metrics
measures
Near-atomic 3D density maps of membrane receptors, ion channels, and drug–target complexes in solution
Core Principles & Analysis
Jacques Dubochet, Joachim Frank, and Richard Henderson were awarded the 2017 Nobel Prize in Chemistry for developing cryo-electron microscopy: plunge-freezing aqueous protein solutions in liquid ethane to embed them in non-crystalline vitreous ice and reconstructing 3D volumes from hundreds of thousands of 2D particle projections.
The "resolution revolution" beginning around 2013 — driven by direct electron-counting detectors and maximum-likelihood motion-correction software — enabled routine 2 to 3.5 Å structure determination without requiring protein crystallization.
Cryo-EM transformed membrane receptor pharmacology by resolving the atomic structures of formerly intractable targets in multiple conformational states, including TRPV1, voltage-gated sodium channels (Nav1.7), ryanodine receptors (RYR2), and GPCR–G-protein complexes.