Frontiers in Cryo Electron Microscopy of Complex Macromolecular Assemblies

Annu Rev Biomed Eng. 2019 Jun 4;21:395-415. doi: 10.1146/annurev-bioeng-060418-052453. Epub 2019 Mar 20.


In recent years, cryo electron microscopy (cryo-EM) technology has been transformed with the development of better instrumentation, direct electron detectors, improved methods for specimen preparation, and improved software for data analysis. Analyses using single-particle cryo-EM methods have enabled determination of structures of proteins with sizes smaller than 100 kDa and resolutions of ∼2 Å in some cases. The use of electron tomography combined with subvolume averaging is beginning to allow the visualization of macromolecular complexes in their native environment in unprecedented detail. As a result of these advances, solutions to many intractable challenges in structural and cell biology, such as analysis of highly dynamic soluble and membrane-embedded protein complexes or partially ordered protein aggregates, are now within reach. Recent reports of structural studies of G protein-coupled receptors, spliceosomes, and fibrillar specimens illustrate the progress that has been made using cryo-EM methods, and are the main focus of this review.

Keywords: G protein–coupled receptor; cryo electron tomography; cryo-EM; fibril; single-particle analysis; spliceosome.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Biomedical Engineering
  • Cryoelectron Microscopy / trends*
  • Electron Microscope Tomography / trends
  • Electron Transport Chain Complex Proteins / chemistry
  • Electron Transport Chain Complex Proteins / ultrastructure
  • Humans
  • Imaging, Three-Dimensional
  • Ion Channels / chemistry
  • Ion Channels / ultrastructure
  • Macromolecular Substances / chemistry*
  • Macromolecular Substances / isolation & purification
  • Macromolecular Substances / ultrastructure*
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / ultrastructure
  • Models, Molecular
  • Spliceosomes / chemistry
  • Spliceosomes / ultrastructure


  • Electron Transport Chain Complex Proteins
  • Ion Channels
  • Macromolecular Substances
  • Membrane Transport Proteins