Advances in high-resolution cryo-EM of oligomeric enzymes

•Atomic models of protein complexes by cryo-EM are now possible.•Structures of proteins that cannot be crystallised can be solved de novo by cryo-EM.•Cryo-EM maps of enzymes can reach resolutions around 2 Å.

Recent advances in cryo-electron microscopy instrumentation and software have made it possible to obtain atomic resolution structures of macromolecular complexes with a small amount of material at low concentration and without the need for crystallisation. Oligomeric enzymes are particularly well suited for this technique because of their symmetry and often large size or rigid structure and can be used to explore the limits of the technique. Conformational changes can reach their full extent in solution, not hampered by crystal contacts, and multiple conformations in a sample can be separated computationally. Cryo-EM structures can be solved de novo for large complexes that resist crystallisation or structure determination by crystallographic techniques.

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