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Introduction: Cryo-EM in Biology and Materials Research

Cite this: Chem. Rev. 2022, 122, 17, 13881–13882
Publication Date (Web):September 14, 2022

Copyright © Published 2022 by American Chemical Society. This publication is available under these Terms of Use.

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This article is part of the Cryo-EM in Biology and Materials Research special issue.

In the year 2012, there were 285 entries in the EM Data Bank reporting structures at resolutions better than 10 Å determined using single particle cryo-EM methods. Icosahedral virus and ribosome structures made up more than half of this set. Representation of smaller protein complexes was minimal; in fact, there were only four entries reporting structures of protein complexes with sizes below 500 kDa at resolutions better than 10 Å.

What a difference a decade makes! As of June 2022, there are >10,000 entries in the EM Data Resource with reported resolutions better than 10 Å, with nearly 2000 entries coming from <500 kDa protein complexes. The overall growth in the number of high-resolution entries of various biological complexes using cryo-EM has been spectacular, with more than 5000 entries deposited that report resolutions better than 4 Å. (These and more statistics are available at

While the resolution advances in the cryo-EM field have been driven by technological advances, the exponential growth in the number of structures deposited over the past decade has been driven by the depth of mechanistic information available from cryo-EM that is difficult to obtain using other structural methods. As a result, cryo-EM methods are being widely adopted by an increasing number of structural biologists, biochemists, and cell biologists, as reflected in the diversity of biological assemblies whose structures are now being analyzed.

In this issue of Chemical Reviews, we bring you a sampling of some of the fascinating applications of cryo-EM to important and challenging problems in modern biology that also have broad applications to the material science community. As highlighted below, the selections cover important methodological advances that have occurred in the field, with applications spanning the range from structures of peptides and membrane proteins to complex biological assemblies, viruses, and filaments.

  • Rodríguez and colleagues illustrate the application of electron diffraction methods such as microED and cRED to obtain structures approaching resolutions of ∼1 Å using thin molecular crystals.

  • Vilas and colleagues provide a historical review of key image processing methods in cryo-EM of protein complexes and also bring us up to date with emerging themes in applying deep learning tools to drive the next generation of methods in this field.

  • Bai and colleagues discuss the exponential surge in cryo-EM structures of single pass transmembrane receptors, a class of proteins that has been largely intractable to X-ray crystallography and NMR approaches.

  • Sexton and colleagues show how a very diverse set of membrane proteins including many biomedically relevant drug targets with sizes ranging from >1 MDa to <100 kDa are now accessible to analysis by cryo-EM at resolutions previously only possible using X-ray crystallography.

  • Chapman and colleagues present a broad overview of cryo-EM studies of adeno-associated virus and show how the structural information that is being obtained is driving applications ranging from use in infectious diseases to gene therapy.

  • Egelman and colleagues present a comprehensive overview of applications of cryo-EM to helical polymers and illustrate how these methods are broadly applicable to biological filaments and self-assembling polymers, and they identify challenges in this exciting field at the intersection of structural biology, materials science, and chemistry.

  • Subramaniam and colleagues provide a detailed overview of the application of cryo-EM and cryo-electron tomographic approaches to SARS-CoV-2 across all stages of the viral life cycle and feature the critical role that cryo-EM is poised to have in the development of effective therapeutics to emerging infectious diseases such as COVID-19.

We hope you enjoy reading this collection of articles that provide a glimpse of the exciting frontiers being explored in biology and material science using cryo-EM and related technologies.

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    • Notes
      Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.


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    Sriram Subramaniam

    Sriram Subramaniam is Gobind Khorana Canada Excellence Research Chair in Cancer Drug Design at the University of British Columbia and also the Founder and CEO of Gandeeva Therapeutics, a drug discovery company based in Vancouver. Prior to his arrival in Vancouver, Sriram was Senior Investigator at the National Institutes of Health, where he also founded and directed the US National Cryo-EM Facility. He received his Ph.D. in physical chemistry from Stanford University and completed postdoctoral training in the Departments of Chemistry and Biology at the Massachusetts Institute of Technology. His work showed for the first time that the structures of proteins, bound drugs, as well as dynamic protein complexes implicated in disease processes could be visualized using cryo-EM methods at resolutions of ∼2 Å. For more information please visit and

    Dganit Danino

    Dganit Danino completed her studies in Chemical Engineering at the Technion – Israel Institute of Technology and then was a postdoctoral fellow at NIDDK, NIH. In 2002 she joined the Faculty of Biotechnology and Food Engineering at the Technion, where she is heading the Cryo-EM Laboratory of Soft Matter. Her research is focused on uncovering mechanisms of self-assembly of soft materials and 1D structures, the development of drug-delivery vehicles, and analyzing the structure and function of milk proteins and large GTPases. She was a visiting scholar at the Physics Department, Harvard University; the Koch Institute, MIT; and the KAVIL Institute for Theoretical Physics, University of California, Santa Barbara. She was the President of the Israel Society for Microscopy (ISM) and the President of the European Colloid and Interface Society (ECIS), and she is a Co-Editor-in-Chief of Current Opinion in Colloid & Interface Science (COCIS) and Editor of Colloids and Surfaces B: Biointerfaces.

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