Chapter 19.9 Four-dimensional cryo-electron microscopy at quasi-atomic resolution: IMAGIC 4D

Crystallography of biological macromolecules

Second Online Edition (2012)

Part 19. Other experimental techniques

  1. M. van Heel1,
  2. R. Portugal1,
  3. A. Rohou1,
  4. C. Linnemayr2,
  5. C. Bebeacua1,
  6. R. Schmidt3,
  7. T. Grant1,
  8. M. Schatz3

Published Online: 14 APR 2012

DOI: 10.1107/97809553602060000875

International Tables for Crystallography

International Tables for Crystallography

How to Cite

van Heel, M., Portugal, R., Rohou, A., Linnemayr, C., Bebeacua, C., Schmidt, R., Grant, T. and Schatz, M. 2012. Four-dimensional cryo-electron microscopy at quasi-atomic resolution: IMAGIC 4D. International Tables for Crystallography. F:19:19.9:624–628.

Author Information

  1. 1

    Faculty of Natural Sciences, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, England

  2. 2

    Division of Internal Medicine, Inflammation Research, University Hospital Zürich, Switzerland

  3. 3

    Image Science Software GmbH, Gillweg 3, D-14193 Berlin, Germany

Publication History

  1. Published Online: 14 APR 2012


The traditional tools of the structural biologist seeking to understand macromolecules and their complexes are X-ray crystallography and NMR spectroscopy. Single-particle cryo-electron microscopy (cryo-EM) has established itself as a new structural-biology technique over the last 15 years. Spectacular insights into the functioning of macromolecular complexes have been achieved especially from combining cryo-EM with the earlier approaches. The resolution levels achieved improved over the last decade from ∼10 Å to sometimes better than ∼4 Å, meaning that a de novo structure determination based on single-particle cryo-EM studies alone is now feasible. More challenging is the new perspective that cryo-EM brings: sorting heterogeneous populations of molecules into individual three-dimensional conformers resulting in sequences of related three-dimensional structures, or in short ‘4D cryo-EM’. Thanks to these developments, single-particle cryo-EM has become the technique of choice for shedding light on the functioning of many a complex biological system. The design of the software instrumentation for 4D cryo-EM is crucial. In this chapter we elaborate on organization issues for single-particle cryo-EM software, as exemplified by recent developments in the IMAGIC 4D software system.


  • cryo-electron microscopy;